Abstract

BackgroundThe prognosis for patients with advanced differentiated thyroid carcinoma (ADTC) with disseminated distant metastases is very poor. Tyrosine kinase inhibitors targeting tumor angiogenesis have been shown to improve progression-free survival in patients with advanced thyroid carcinoma and progressive radioiodine-refractory thyroid carcinoma. Tyrosine kinase inhibitor has been reported as a successful neoadjuvant for total thyroidectomy to reduce tumor burden. However, the special indications for prompt treatment with lenvatinib as a rescue therapy to reduce tumor burden and prolong a durable response to radioiodine therapy have not been explored.Case presentationHere, we present two ADTC cases with distant metastases who were effectively treated by total thyroidectomy combined with lenvatinib to prolong a durable response to radioiodine therapy. Case 1 was a 66-year-old male diagnosed with ADTC and disseminated brain, lung, and bone metastases. Lenvatinib was initiated via compassionate access because of rapidly progressive tumor growth even after second doses of radioiodine therapy and external beam radiation therapy for his brain metastases. The result was a durable response to lenvatinib, slowing progressive tumor growth for 3 years and allowing a third course of radioiodine therapy to treat the bone metastases. Case 2 was a 45-year-old male diagnosed with ADTC and diffuse disseminated lung metastases. Respiratory failure ensued after total thyroidectomy, requiring mandatory support by respirator. Lenvatinib was started as a rescue therapy to reduce tumor burden rapidly. The patient was successfully weaned off the respirator only 1 week after using lenvatinib. The patient was then maintained on a low dose of lenvatinib, allowing three subsequent courses of radioiodine therapy. Currently, his lung metastasis remains well controlled with decreased lung infiltrating nodules and the patient can tolerate exercise well.ConclusionOur case experience indicated that lenvatinib has significant value as salvage therapy, reducing tumor burden, producing a durable response and maintaining quality of life. For ADTC patients with progressive life-threatening metastases, our experience suggests that lenvatinib treatment can be used as an urgent rescue therapy as well as a complement to radioiodine therapy to improve tumor eradication.

Highlights

  • The prognosis for patients with advanced differentiated thyroid carcinoma (ADTC) with disseminated distant metastases is very poor

  • Progressive multiple hit theory is used to model the difference between well-differentiated thyroid carcinoma (WDTC), ADTC, Poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid carcinoma (ATC)

  • WDTC is initiated by a mutation or rearrangement in the mitogen-activated protein kinase (MAPK) or Pax8-PPAR signaling pathways and additional mutations (PI3K/PTEN, Akt, P53), gene amplifications (EGFR, VEGFR), or epigenetic silencing results in progression to more aggressive ADTC, PDTC, or ATC disease [1, 2, 9]

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Summary

Conclusion

Our case experience indicated that lenvatinib has significant value as salvage therapy, reducing tumor burden, producing a durable response and maintaining quality of life.

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Funding None
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