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Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in children and adolescents. Infrequently, children with PTC may present with or develop disease not amenable to surgery or radioactive iodine (RAI), and systemic therapy may be an option. Lenvatinib is an oral tyrosine kinase inhibitor that is approved by the Food and Drug Administration for the treatment of adults with locally recurrent or metastatic, progressive, RAI-refractory well-differentiated thyroid carcinoma. The effect of lenvatinib in children with PTC has not been reported. Patient findings: Three children with metastatic PTC not amenable or refractory to RAI who responded to lenvatinib are reported. All of them developed respiratory distress requiring oxygen caused by extensive bilateral metastatic pulmonary disease. The first patient is a 14-year-old female who was initially treated with sorafenib for extensive PTC not amenable to upfront surgery or RAI. She had progressive pulmonary disease after five months, and was subsequently treated with oral lenvatinib (14 mg/m2/day). She was weaned to room air after eight weeks. The second patient is a 15-year-old male who was treated with lenvatinib (14 mg/m2/day) for iodine non-avid diffuse pulmonary disease after initial total thyroidectomy and cervical lymph node dissection. He was weaned off oxygen in six weeks. The third patient is a five-year-old male who was treated with lenvatinib (14 mg/m2/day) for pulmonary disease progression 24 months after treatment with total thyroidectomy, cervical lymph node dissection, and RAI treatment. He was weaned off oxygen one day after starting lenvatinib. Two of the patients required dose adjustments secondary to proteinuria. Otherwise, all patients tolerated lenvatinib well. The first two patients remained clinically stable on lenvatinib 23 months and 11 months after initiation of therapy, respectively, and the third patient transitioned to a tumor-specific targeted therapy after one month. Summary: Three pediatric patients are reported with metastatic PTC not amenable or refractory to RAI who achieved a response on lenvatinib. Conclusion: Lenvatinib therapy is well tolerated and demonstrated clinical activity in children with advanced PTC. Lenvatinib should be considered in children with PTC that is refractory or not amenable to conventional management. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX) uptake is mediated by the reduced folate carrier (RFC). Defective drug uptake in association with decreased RFC expression is a common mechanism of MTX resistance in many tumor types. Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells, its role and prevalence in RFC transcription regulation are, however, not widely studied. Methods: In the current study, RFC promoter methylation was assessed using methylation specific PCR in a panel of malignant cell lines (n = 8), including MDA-MB-231, and M805, a MTX resistant cell line directly established from the specimen of a patient with malignant fibrohistocytoma, whom received multiple doses of MTX. A quantitative approach of real-time PCR for measuring the extent of RFC promoter methylation was developed, and was validated by direct bisulfite genomic sequencing. RFC mRNA levels were determined by quantitative real-time RT-PCR and were related to the extent of promoter methylation in these cell lines. Results: A partial promoter methylation and RFC mRNA down-regulation were observed in M805. Using the quantitative approach, a reverse correlation (correlation coefficient = -0.59, p < 0.05) was identified between the promoter methylation and RFC mRNA levels in this a panel of malignant cell lines. Conclusion: This study further suggests that promoter methylation is a potential basis for MTX resistance. The quantitative correlation identified in this study implies that promoter methylation is possibly a mechanism involved in the fine regulation of RFC transcription. [ABSTRACT FROM AUTHOR]

Primary osseous tumors of the spinal column account for approximately 1% of the total number of spinal tumors found in the pediatric patient population. The authors present a case of a C1 benign giant cell lesion that was incidentally found in a 15-year-old patient. A transoral biopsy was performed followed by treatment with denosumab, with definitive management in the form of transoral tumor resection with subsequent occiput-cervical three posterior instrumented fusion. The patient tolerated all of the procedures well, as there were no post-operative complications, discharged home neurologically intact and was eager to return to school when assessed during a follow-up visit in clinic. Osteolytic lesions affecting the cervical spine are rare in the pediatric population. It is of utmost importance to have sufficient background knowledge in order to formulate a differential diagnosis, as well as an understanding of principles underlying surgical techniques required to prevent occipital-cervical instability in this patient population. The information presented will guide surgical decision-making by identifying the patient population that would benefit from neurosurgical interventions to stabilize the atlantoaxial junction, in the context of rare osteolytic conditions affecting the cervical spine. [ABSTRACT FROM AUTHOR]