Mutation-based, neoadjuvant treatment for advanced anaplastic thyroid carcinoma
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Frontiers Media SA
Abstract
Introduction: The prognosis of anaplastic thyroid carcinoma (ATC) remains poor.
Mutation-based targeted therapies and immune checkpoint inhibitors (ICI) have
gained increasing importance in the treatment of advanced tumor stages. This
study aimed to investigate whether mutation-based neoadjuvant therapy can
convert an initially unresectable tumor into a resectable state, optimizing local
tumor control and prolonging overall survival.
Methods: Patients with stages IVB and limited IVC BRAFV600E-negative ATC
received immediate combination therapy consisting of the multikinase inhibitor
(mKI) lenvatinib and the immune checkpoint inhibitor (ICI) pembrolizumab upon
diagnosis. Patients with BRAFV600E-positive tumors were treated with a BRAF/
MEK inhibitor regimen, consisting of dabrafenib and trametinib. This neoadjuvant
therapy was administered for 4–6 weeks before re-staging. If FDG-PET/CT
imaging demonstrated tumor regression, surgical resection of the primary
tumor was performed. In cases of limited distant metastases, these were also
surgically removed. In the adjuvant setting, mutation-based systemic therapy
was continued.
Results: Between December 2021 and December 2024, a total of 14 patients
were screened. Ultimately, 12 patients, with a median age of 73 years (range: 54–
85), were treated with neoadjuvant therapy. At diagnosis, six patients had UICC
stage IVB and six stage IVC ATC. A BRAFV600E-mutation was detected in two
patients. Following neoadjuvant therapy, eight patients showed tumor
regression, whereas three exhibited an inadequate response, characterized by
disease progression or a mixed response on FDG-PET/CT. In one patient, therapy
was discontinued early due to severe local symptoms. During neoadjuvant
treatment, two cases of tracheoesophageal or tracheocutaneous fistulas were
observed. Surgical resection was performed in nine patients. An R0 resection was
achieved in two, an R1 resection in six, and an R2 resection in one patient. The
median follow-up period was eight months (range 1–36). Median progressionfree survival (PFS) was three months (range 1–not reached), while median overall
survival (OS) was nine months (range 1–not reached).
Conclusion: Neoadjuvant therapy for advanced ATC appears to be a promising
treatment approach for a subset of affected patients. While initial results are
encouraging, further research is needed to establish its precise role within the
multimodal management of this aggressive malignancy.
Metadata
Philipps-Universität Marburg
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Except where otherwise noted, this item's license is described as Attribution 4.0 International