Anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC), also known as anaplastic thyroid carcinoma, is an aggressive form of thyroid cancer characterized by uncontrolled growth of cells in the thyroid gland. This form of cancer generally carries a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. The cells of anaplastic thyroid cancer are highly abnormal and usually no longer resemble the original thyroid cells and have poor differentiation. ATC is an uncommon form of thyroid cancer only accounting for 1 2% of cases, but due to its high mortality, is responsible for 20 50% of deaths from thyroid cancer. The median survival time after diagnosis is three to six months. It occurs more commonly in women than in men and is seen most commonly in people ages 40 to 70. Cellular death is frequently visualized on microscopic images. There are no reliable laboratory tests for ATC. A multidisciplinary team including an endocrine pathologist, head and neck surgeon, medical oncologist, radiation oncologist, endocrinologist, and a palliative care physician is essential for optimal management. a type of medication that selectively destroys tumor blood vessels, clinical trials have been evaluating whether the medication can extend the survival of patients with ATC. With the advent of molecular testing and next generation sequencing, BRAF and MEK inhibitors are playing an increasing role in the management of patients with anaplastic thyroid cancer harboring such mutations. The combination of dabrafenib and trametinib has shown significant increases in overall survival and has been approved by the FDA. Another similar combination is vemurafenib and cobimetinib. Immunotherapy is also starting to play an important role in anaplastic thyroid cancer management with several ongoing clinical trials demonstrating promising effects. Specific drugs being tested are atezolizumab, pembrolizumab, and spartalizumab, amongst others. Combinatorial therapy that is molecular based may lead to significant tumor regression, potentially making patients amenable to curative surgery.

The role of external beam radiotherapy (EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended. The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomized controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine avid cancer. Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non treatment groups in the use of radio iodine and post treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies. Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small. Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first line treatment.

In the absence of extracervical or unresectable disease, surgical excision should be followed by adjuvant radiotherapy. In the 18–24% of patients whose tumour seems both confined to the neck and grossly resectable, complete surgical resection followed by adjuvant radiotherapy and chemotherapy could yield a 75–80% survival at 2 years. There are a number of clinical trials for anaplastic thyroid carcinoma underway or being planned.