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Advances in the management of anaplastic thyroid carcinoma: transforming a life-threatening condition into a potentially treatable disease

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Abstract

Anaplastic thyroid cancer (ATC) is an infrequent thyroid tumor that usually occurs in elderly patients. There is often a history of previous differentiated thyroid cancer suggesting a biological progression. It is clinically characterized by a locally invasive cervical mass of rapid onset. Metastases are found at diagnosis in 50% of patients. Due to its adverse prognosis, a prompt diagnosis is crucial. In patients with unresectable or metastatic disease, multimodal therapy (chemotherapy and external beam radiotherapy) has yielded poor outcomes with 12-month overall survival of less than 20%. Recently, significant progress has been made in understanding the oncogenic pathways of ATC, leading to the identification of BRAF V600E mutations as the driver oncogene in nearly 40% of cases. The combination of the BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) showed outstanding response rates in BRAF-mutated ATC and is now considered the standard of care in this setting. Recently, it was shown that neoadjuvant use of DT followed by surgery achieved 24-month overall survival rates of 80%. Although these approaches have changed the management of ATC, effective therapies are still needed for patients with BRAF wild-type ATC, and high-quality evidence is lacking for most aspects of this neoplasia. Additionally, in real-world settings, timely access to multidisciplinary care, molecular testing, and targeted therapies continues to be a challenge. Health policies are warranted to ensure specialized treatment for ATC.

The expanding knowledge of ATC´s molecular biology, in addition to the ongoing clinical trials provides hope for the development of further therapeutic options.

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Abbreviations

ATA:

American Thyroid Association

ATC:

Anaplastic thyroid carcinoma

CR:

Complete response

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DT:

Dabrafenib + trametinib

DTC:

Differentiated thyroid carcinoma

EBRT:

External beam radiation

ESMO:

European society of medical oncology

FDA:

Food and Drug Administration

HR:

Hazard ratio

CI:

Confidence interval

ICI:

Immune checkpoint inhibitors

IHC:

Immunohistochemistry

NCCN:

National Comprehensive Cancer Network

NGS:

Next generation sequencing

ORR:

Overall response rate

OS:

Overall survival

PD-1:

Cell death protein 1

PD-L1:

Programmed cell death ligand 1

PDTC:

Poorly differentiated thyroid cancer

PFS:

Progression free survival

PR:

Partial response

PTC:

Papillary thyroid carcinoma

RR:

Relative risk

TMB:

Tumor mutation burden

WHO:

World Health Organization

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Authors and Affiliations

  1. Endocrinology Division, Instituto de Oncología AH Roffo, University of Buenos Aires, Buenos Aires, Argentina

    Inés Califano

  2. Endocrinology Division, Instituto de Investigaciones Médicas A. Lanari, University of Buenos Aires, Buenos Aires, Argentina

    Anabella Smulever

  3. Endocrinology Division, Hospital de Clínicas, University of Buenos Aires, Buenos Aires, Argentina

    Fernando Jerkovich & Fabian Pitoia

Authors
  1. Inés Califano
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  2. Anabella Smulever
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  3. Fernando Jerkovich
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  4. Fabian Pitoia
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Contributions

All authors contributed to the study conception and design. Literature search and data analysis was made by all authors. IC, AS, FJ, and FP wrote the main manuscript text. FJ and AS prepared Tables 1, 2, 3 and 4. IC and AS prepared Figs. 1, 2 and 3. All authors reviewed and approved the final manuscript.

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Correspondence to Inés Califano.

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Conflict of interest

Fabián Pitoia: principal investigator in multicenter studies for Bayer, Exelixis, Novartis. Speaker for Bayer. Inés Califano: investigator in multicenter studies for Novartis. Speaker for Bayer, Biotoscana/Knightt. Anabella Smulever and Fernando Jerkovich have no conflicts of interest relevant to the content of this article.

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Califano, I., Smulever, A., Jerkovich, F. et al. Advances in the management of anaplastic thyroid carcinoma: transforming a life-threatening condition into a potentially treatable disease. Rev Endocr Metab Disord 25, 123–147 (2024). https://doi.org/10.1007/s11154-023-09833-1

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