Major Research Findings

Significant improvements have been made in the outcomes of children with cancer, but the pace of improvement has slowed in recent years. The limits of therapy intensification may have been reached for many pediatric cancers. With increasing numbers of pediatric cancer survivors, the long-term side effects of treatment have become increasingly apparent. Therefore, attention has shifted to the use of molecularly targeted agents and immunotherapies to improve the outcomes of children who are not cured by traditional cytotoxic chemotherapies and to decrease exposure to cytotoxic chemotherapy and reduce late effects. 4

While thyroid nodules have relatively low incidence in children and adolescents, they are at high risk of malignancy. In addition, the clinical manifestations, biological behaviors, assessment methods, indications of fine-needle aspiration, and treatment principles also differ from those in adults. In the past, the assessment, treatment, and follow-up of thyroid nodules in children and adolescents followed the guidelines for adult patients, which are actually not applicable for children and adolescents in the real-world clinical settings. Based on the latest international guidelines on the management of thyroid nodules and differentiated thyroid cancer, this article summarizes the clinical features, pathological characteristics, evaluation methods, treatments, and follow-up of thyroid cancer in children and adolescents. 5

The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. This study compares studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima to cohorts without radiation exposure of those two countries. Radiation-induced DTC may be characterized by a lag time of 4-5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g. nitrate are required to quantify their combined effect on thyroid cancer risk. 3

Treatment Summary

Therapy-related acute myeloid leukemia (t-AML) has a dismal prognosis and is one of the most frequent second malignant neoplasms which could be encountered by pediatric oncologists. Between October 2000 and September 2016, 16 patients who had primary solid tumors were diagnosed with t-AML at the Seoul National University Children's Hospital. The median patient age at the time of diagnosis of their primary solid tumors was 9.6 years (range, 0.1 to 15.4 y), and that of t-AML was 14.0 years (range, 4.7 to 23.9 y). The median latency period from the end of the primary tumor treatment to the initial diagnosis of t-AML was 29 months (range, 6 to 130 mo). Twelve patients achieved complete remission. Of them, only 7 patients underwent hematopoietic stem cell transplantation (HSCT). The 3-year overall survival (OS) rates and event-free survival rates were 33.7±12.2% and 26.9±11.5% respectively. The patients who underwent HSCT showed favorable 5-year OS rates (57.1±18.7%), whereas the 5-year OS rates of those who did not undergo HSCT was 0%. This study demonstrates that an achievement of complete remission and a subsequent HSCT can be the optimal solution for the treatment of t-AML, and this strategy showed acceptable outcomes. 6

Benefits and Risks

Benefit Summary

A major benefit of cancer treatment in children is improved survival rates. Advances in treatment have enabled many children to recover from cancer and live healthy lives. 4

Risk Summary

Cancer treatment in children can have side effects such as nausea, vomiting, hair loss, fatigue, and increased risk of infection. Long-term side effects may include heart disease, infertility, and cognitive impairment. 4

Comparison Between Studies

Commonalities of Studies

Multiple studies highlight the potential value of molecularly targeted agents and immunotherapies in the treatment of childhood cancer. 4

Differences of Studies

Studies focus on specific types of cancer, treatment methods, and patient characteristics. For example, some studies focus on immunotherapy in the treatment of leukemia, while others focus on molecularly targeted agents for solid tumors. 4

Consistency and Contradictions of Findings

While studies support the promise of molecularly targeted agents and immunotherapies in childhood cancer treatment, further research is needed to determine the optimal use of these therapies. 4

Notes on Applying Research in Real Life

Cancer treatment options for children vary depending on the specific type of cancer, age, health status, and other factors. It is important to consult with a doctor or healthcare professional for the latest information and recommendations on childhood cancer treatment. 4

Current Research Limitations

Research on cancer treatment for children is ongoing, and long-term outcomes are not yet fully understood. 4

Future Research Directions

Additional research is needed to investigate the long-term effectiveness and safety of molecularly targeted agents and immunotherapies. Also, the potential of combining these therapies with other treatments to further improve treatment outcomes should be explored. 4

Conclusion

Cancer treatment for children has made significant progress in recent years, with improved survival rates. However, the limits of therapy intensification may have been reached for many pediatric cancers, and the pace of improvement has slowed. Also, with increasing numbers of pediatric cancer survivors, the long-term side effects of treatment have become increasingly apparent. Therefore, attention has shifted to the use of molecularly targeted agents and immunotherapies to improve the outcomes of children who are not cured by traditional cytotoxic chemotherapies and to decrease exposure to cytotoxic chemotherapy and reduce late effects. Additional research is needed to investigate the long-term effectiveness and safety of molecularly targeted agents and immunotherapies. Also, the potential of combining these therapies with other treatments to further improve treatment outcomes should be explored. It is important to consult with a doctor or healthcare professional for the latest information and recommendations on childhood cancer treatment. 4

Treatment List

Cytotoxic chemotherapy, molecularly targeted agents, immunotherapy, hematopoietic stem cell transplantation, radioactive iodine therapy, surgery