Update on current diagnosis and management of anaplastic thyroid carcinoma

Abstract

Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%. However, the undifferentiated or anaplastic type accounting for < 0.2%, usually in elderly individuals, exhibits a dismal prognosis with rapid growth and disappointing outcomes. It is the most aggressive form of thyroid carcinoma, with a median survival of 5 mo and poor quality of life (airway obstruction, dysphagia, hoarseness, persistent pain). Early diagnosis and staging are crucial. Diagnostic tools include biopsy (fine needle aspiration, core needle, open surgery), high-resolution ultrasound, computed tomography, magnetic resonance imaging, [(18)F]fluoro-D-glucose positron emission tomo-graphy/computed tomography, liquid biopsy and microRNAs. The BRAF gene (BRAF-V600E and BRAF wild type) is the most often found molecular factor. Others include the genes RET, KRAS, HRAS, and NRAS. Recent management policy is based on surgery, even debulking, chemotherapy (cisplatin or doxorubicin), radiotherapy (adjuvant or definitive), targeted biological agents and immunotherapy. The last two options constitute novel hopeful management modalities improving the overall survival in these otherwise condemned patients. Anti-programmed death-ligand 1 antibody immunotherapy, stem cell targeted therapies, nanotechnology achievements and artificial intelligence imple-mentation provide novel promising alternatives. Genetic mutations determine molecular pathways, thus indicating novel treatment strategies such as anti-BRAF, anti-vascular endothelial growth factor-A, and anti-epidermal growth factor receptor. Treatment with the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has been approved by the Food and Drug Administration in cases with BRAF-V600E gene mutations and is currently the standard care. This neoadjuvant treatment followed by surgery ensures a two-year overall survival of 80%. Prognostic factors for improved outcomes have been found to be younger age, earlier tumor stage and radiation therapy. A multidisciplinary approach is necessary, and the therapeutic plan should be individualized based on surveillance and epidemiology end results.

Keywords: Thyroid diseases; Thyroid cancers; Anaplastic carcinoma; Undifferentiated carcinoma; Neck mass; Aggressive malignancies

Core Tip: Anaplastic thyroid carcinoma is uncommon but one of the most lethal neoplasms. The optimal management remains unclear. The addition of novel targeted therapy and immunotherapy to the traditional management of surgery, radiation and chemotherapy has improved the outcomes. Multimodality management and the emerging use of individualized treatment based on novel therapeutic agents offers promising results. However, further research efforts involving the molecular microenvironment and biological drivers should be made.