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Initial Treatment of BRAF V600E-Variant Anaplastic Thyroid Cancer
Anaplastic thyroid cancer (ATC) is an aggressive variant of thyroid cancer that used to be universally fatal. BRAF V600E mutation is observed in approximately 10% to 50% of patients with ATC; in 2018, the combination of dabrafenib and trametinib (DT) was approved by the FDA based on promising results of a phase 2 study (J Clin Oncol 2018; 36:7) and transformed the care of patients with BRAF V600E-mutated ATC.
A new consensus statement on treatment and management of BRAF V600E-mutated ATC emphasizes rapid identification of BRAF status by immunohistochemistry or polymerase chain reaction followed by timely initiation of systemic therapy. The Thyroid Neck Morbidity Complexity (TNMC) score is used to determine whether neoadjuvant treatment is needed. The proposed algorithm for initial management of stage IVb ATC involves neoadjuvant DT or pembrolizumab + DT (DTP) for patients with unresectable or advanced disease (TNMC ≥1), while patients without radiographic evidence of extrathyroidal or extranodal extension (TNMC 0) should proceed with upfront surgery.
The authors favor DTP over DT, as it was associated with better overall survival (Thyroid 2024; 3:336), but the addition of pembrolizumab can be delayed, as the extent of tumor shrinkage is mainly dependent on the use of DT. After 2 to 3 months of neoadjuvant therapy, patients should be reassessed for resectability with contrast-enhanced computed tomography or PET/CT then treated surgically if feasible. DT(P) should be withheld during adjuvant chemoradiation, then can be resumed after completion of radiation.
For stage IVc ATC with distant metastasis, once brain metastasis is ruled out, the authors recommend starting DTP. Patients should also be considered for surgery if the disease is resectable after 2 to 3 months of systemic therapy. Complete resection of the primary tumor should be considered because it improves the quality of life, prevents complications, and prolongs survival even in patients with distant metastasis.
Comment
This consensus statement presents clinical practice standards and recommendations from a multidisciplinary team at a large academic cancer center. The statement does not contradict the current guidelines from the American Thyroid Association and the National Comprehensive Cancer Network, but it does describe a complex treatment pathway that may require multidisciplinary care. Certain components of the pathway (e.g., adding pembrolizumab to DT) are based on weaker evidence from retrospective clinical data. Nonetheless, the statement provides valuable insights and practical guidance on management of patients with complex ATC.
Citation(s)
Author:
Hamidi S et al.
Title:
Initial management of BRAF V600E-variant anaplastic thyroid cancer: The FAST multidisciplinary group consensus statement.
Source:
JAMA Oncol
2024
Sep
1; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Hyunseok Kang, MD, MPH, FACP