Anaplastic Thyroid Carcinoma Follow-up
- Author: Anastasios K Konstantakos, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC more...
Further Inpatient Care
The role of adjuvant therapy in anaplastic thyroid carcinoma (ATC) has not been clearly defined. Radiotherapy and chemotherapy regimens continue to be investigated.
Despite the fact that ATC is largely radioresistant, external-beam radiotherapy is used for local control. Some evidence shows that hyperfractionation may lead to better success at local control by permitting delivery of higher doses of total radiation with less toxicity.
Bhatia et al reported on the use of conformal 3-dimensional radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT) in 53 consecutive patients with anaplastic thyroid cancer. Median radiation dose was 55 Gray (Gy; range, 4-70 Gy); IMRT was given to a median 60 Gy (range, 39.9-69.0 Gy). Superior survival was noted in patients without distant metastases who received ≥50 Gy.
Currently, no available chemotherapeutic agent or combination of chemotherapeutic agents shows sufficient antineoplastic activity to prevent death; yet, in rare instances, chemotherapy may prolong life by a few weeks or perhaps months. Doxorubicin and cisplatin are the two most commonly used agents; however, resistance from cellular extrusion of the drugs occurs. Valproic acid has been introduced into treatment regimens because it induces apoptosis, modulates differentiation gene expression of thyroid tumors, and enhances the sensitivity of anaplastic cancer cell lines to doxorubicin.
A study from the Netherlands reported significantly improved local control and improved median survival with a protocol consisting of locoregional radiotherapy in 46 fractions of 1.1 Gy, given twice daily, followed by prophylactic irradiation of the lungs in 5 daily fractions of 1.5 Gy. Low-dose doxorubicin (15 mg/m2) is administered weekly during radiotherapy, followed by adjuvant doxorubicin (50 mg/m2) 3 times a week up to a cumulative dose of 550 mg/m2.
Since ATC is a relatively uncommon disease, large phase III clinical trials of systemic therapies are not possible to perform. For that reason, the value of newer therapies, such as taxanes, gemcitabine, and irinotecan, and targeted therapies, such as receptor tyrosine kinase inhibitors, is unknown.
Immunohistochemical evaluation of molecular markers in ATC showed frequent and strong overexpression of beta-catenin, aurora A, cyclin E, cyclin D1, and epidermal growth factor receptor. These findings support the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors.
Wagle and colleagues reported an 18-month response to everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), in a patient with metastatic anaplastic thyroid carcinoma. Resistance to everolimus developed as a result of a mutation in MTOR conferring resistance to allosteric mTOR inhibition. The mutation remained sensitive to mTOR kinase inhibitors.
See the list below:
Risk of local complications from thyroid surgery (eg, permanent hypoparathyroidism, recurrent laryngeal nerve palsy) may be increased with anaplastic thyroid carcinoma (ATC) if aggressive resection is attempted.
With limited thyroid resection, incidence of these local complications should not be significantly greater.
ATC may cause airway obstruction. Patients with impending airway obstruction who are not candidates for local resection or chemoradiation should undergo tracheostomy; interventional bronchoscopy, including Nd-YAG laser and airway stenting, is an alternative to surgery in inoperable cases. 
Anaplastic thyroid carcinoma (ATC) typically has a rapidly progressive course. The overall 5-year survival rate is reportedly less than 10%, and most patients do not live longer than a few months after diagnosis.
One study has shown that patients younger than 60 years who have ATC confined to the thyroid have a better prognosis than patients who are older and have distant metastases. A retrospective study from Korea found that age less than 60 years, tumor size less than 7 cm, and lesser extent of disease were independent predictors of lower disease-specific mortality.
While some studies have suggested that postoperative radiotherapy may be of benefit in terms of survival, definitive prospective trials are lacking.
Akaishi et al conducted a review of 100 patients with ATC in a single hospital (Ito Hospital) from 1993-2009. The 1-year survival rates were as follows:
Stage IVA - 72.7%
Stable IVB- 24.8%
Stable IVC - 8.2%
Multivariate analysis demonstrates worse prognosis with age older than 70 years, WBC count of 10,000 mcL or more, extrathyroidal invasion, and distant metastases at the time of diagnosis. Survival was significantly better if the patient received complete resection or external radiation at doses of 40 Gy or more. Prognosis remains poor among patients with ATC, but complete surgery, radiotherapy, and a combination of the 2 modalities improved the survival of patients.
Orita et al developed a prognostic index that can predict prognosis and assist in the early treatment of ATC.
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