Cultural Differences Drive Kids' Thyroid Cancer Management

Liam Davenport


December 07, 2022

The recent European Thyroid Association (ETA) guidelines on the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) emphasized the need for individualized and multidisciplinary care.

As reported by Medscape Medical News, they also underlined the need for the comprehensive evaluation of patients and ongoing follow-up, all of which underscore the challenges of managing this population.

Although the ETA guidelines were based around the 2015 American Thyroid Association (ATA) guidelines, a recent presentation at the ATA 2022 meeting on sparing radioactive iodine (RAI) therapy in low-risk pediatric patients with DTC highlighted some of the differences between the two documents, and their clinical implications.

To find out more, Medscape Diabetes & Endocrinology caught up with Chantal A. Lebbink, PhD student, Department of Pediatric Endocrinology, and Hanneke M. van Santen, MD, Pediatric Endocrinologist and Associate Professor, Wilhelmina Children's Hospital, Utrecht, the Netherlands, the lead and senior authors, respectively, of the ETA guidelines.

How is pediatric DTC different from that in adults?

There are important differences between adult and pediatric DTC in terms of their clinical, molecular, and pathologic characteristics.

Compared with adults, pediatric patients with DTC more often present with advanced disease at diagnosis, including more lymph node involvement, distant metastasis, and multifocal disease. Yet despite this more aggressive presentation, pediatric DTC has an excellent prognosis.

Another difference is that the most common genetic alterations in pediatric DTC are RET-PTC and NTRK fusions, whereas mutations in BRAF V600E and RAS point mutations are less frequent. This means that the utility of molecular testing on thyroid nodule biopsies and on thyroid tissue in children may be different from that in adults.

Finally, the consequences of possible adverse effects of treatment may be different for children owing to their longer life expectancy.

What are the main challenges in treating DTC in the pediatric population?

The biggest challenge is tailoring the therapy to find a balance between overtreatment and undertreatment.

In children presenting with advanced disease, total thyroidectomy with central and/or lateral lymph node dissection and RAI therapy might be beneficial. However, in those with a small low-invasive tumor and no metastases, total thyroidectomy alone, or even just lobectomy, might be sufficient.

Saying that, the evidence for stratifying which tumor, in terms of its clinical, pathologic, and molecular characteristics, is associated with more advanced or low-invasive disease is scarce. 

Additionally, the benefit of more "aggressive" treatment needs to be weighed against the harm of possible adverse effects, such as surgical complications and those due to RAI therapy.

Especially in children, the psychological impact of treatment must also be considered.

Choosing the optimal treatment approach is therefore complex and cannot be generalized, because of variations in the individual presentation, risk factors, and prognosis.

Overall, children with DTC should be stratified into those who may benefit from higher-intensity treatment vs those in whom lower-intensity treatment will suffice, regardless of whether they have high- or low-risk disease.

How variable is the care of pediatric DTC across Europe, and how did that inform the ETA guidelines?

The organization of care for children with DTC differs between countries across Europe. These include differences in which medical specialist is ultimately responsible for the management and treatment of these children. In the Netherlands, a pediatric endocrinologist is most often the responsible medical specialist, whereas in the UK it may be the pediatric oncologist, and in Germany the nuclear physician.

In our opinion, such differences do not necessarily impact the quality of care, but it depends on the expertise of the treating physician and its team.

Above all, we recommend that a child with, or suspected of having, thyroid carcinoma should be referred to an experienced multidisciplinary thyroid team, specifically with experience in pediatric care. The multidisciplinary team should include a pediatric and an adult endocrinologist, a pediatric radiologist, a high-volume pediatric surgeon experienced in thyroid surgery, a pathologist, a nuclear medicine physician, a clinical geneticist, a pediatric psychologist, and a pediatric oncologist. 

Because DTC in children is a rare disease, centralization of care to expert centers is an important step in improving management and outcomes. However, although a reduction in the number of hospitals might not drastically harm accessibility at a population level, it may present challenges for children living in rural areas.

If centralization is not possible for whatever reason, consultation with the expert team is mandatory, and this can be achieved via online meetings.

In the Netherlands, for example, we have started a 3-monthly online multidisciplinary board meeting, at which all Dutch patients are discussed. This improves national collaboration and harmonizes treatment.

What are the key differences between the ETA and ATA guidelines?

The main ones are cultural, particularly regarding the surgical approach, nuclear medicine regulations, and patient follow-up.

Differences in the regulations regarding nuclear medicine between Europe and the US have resulted in differences in the recommendations on the use of RAI therapy.

For example, the ATA 2015 guidelines suggest no iodine treatment in low-risk patients. The guidelines were evaluated by Bauer and colleagues, and they concluded that withholding RAI therapy does not have a negative impact on remission.

However, the surgical approach should also be taken into account.

The ATA guidelines recommend that, for patients with no clinical evidence of gross extrathyroidal invasion and/or locoregional metastasis, prophylactic central lymph node dissection (CLND) may be selectively considered on the basis of tumor focality and size, and the experience of the surgeon.

But the use of prophylactic CLND is debatable in both children and adults. The benefits must be weighed against the risk for missing clinically significant disease during preoperative ultrasound or intraoperative assessment, and of postoperative complications.

The ETA expert panel therefore suggests that CLND can be avoided or limited to ipsilateral lymphadenectomy in patients without features indicative of advanced thyroid cancer on neck ultrasound and be reserved for advanced thyroid cancer only.

In other words, the panel suggests more reluctance to prophylactic CLND, because of the potential for postoperative complications, but recommends RAI therapy for all patients, owing to the high rate of lymph node metastases.

As mentioned before, however, an individualized treatment approach, regardless of the patient's level of risk, is important.

In terms of the optimal follow-up, the European approach tends to be less "aggressive," recommending less imaging vs that in the US and no standard diagnostic whole-body scans.

The ATA are preparing an updated version of their guideline. Do you expect there will be greater convergence in the recommendations between the two guidelines?

Evidence on management and treatment of thyroid nodules and DTC in children is limited. This was the case in 2015 and, unfortunately, still is the case in 2022.

In the ETA guidelines, 84% of the suggestions or recommendations are based on low-quality evidence, including expert opinion. As Bauer and colleagues suggested, expert panels are therefore forced to decide whether to base their recommendations solely on existing studies or to deviate from published literature so as to innovate and to address practice needs for which no, or inadequate, literature exists.

The ETA recommendations are, and the updated ATA recommendations will be, based on the current literature. However, differences in medical regulations between Europe and the Unites States still exist, and expert opinion will play a role in the degree of convergence.

Lebbink and Santen have declared no relevant financial relationships.

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