Anaplastic Thyroid Carcinoma Treatment & Management

Updated: May 08, 2018
  • Author: Anastasios K Konstantakos, MD; Chief Editor: Neetu Radhakrishnan, MD  more...
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Treatment

Approach Considerations

Treatment of anaplastic thyroid carcinoma (ATC) is mostly palliative. Surgical resection with adjuvant radiation therapy and chemotherapy may prolong survival somewhat and improve quality of life. The role of adjuvant therapy in ATC has not been clearly defined. Radiotherapy and chemotherapy regimens continue to be investigated. 

Consider patients with unresectable tumors who are in good general condition for phase I studies, which represent the only opportunity to identify drugs with some activity against this uncommon disease. These studies are available in any major cancer center, are generally financed by the industry, and may help individual patients.

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Medical Care

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 (ATC). 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. [15]

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. [16]

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. [17]

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.

In May 2018, the US Food and Drug Administration (FDA) approved dabrafenib in combination with trametinib for locally advanced or metastatic ATC with the BRAF V600E mutation in patients with no satisfactory locoregional treatment options. Approval was based on the BRF117019 study (NCT02034110), in which 57% of the 23 evaluable patients in the ATC cohort achieved a partial response and 4% reached a complete response; 645 of responses lasted for 6 months or longer. BRF117019 was a nine-cohort, multicenter, nonrandomized, open-label trial in patients with rare cancers with the BRAF V600E mutation. [18, 19]

Immunohistochemical evaluation of molecular markers in ATC has shown frequent and strong overexpression of beta-catenin, aurora A, cyclin E, cyclin D1, and epidermal growth factor receptor (EGFR). These findings support the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors. [20]

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. [11]

 

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Surgical Care

Use surgery to obtain a definitive diagnosis when fine-needle aspiration is unsuccessful. Surgery is performed in conjunction with radiation and chemotherapy. An early prophylactic tracheostomy may be required for protection of the airway during surgery.

Despite the typically large size of these tumors, the extent of resection is limited when the diagnosis is made. Rather than performing complete thyroidectomy, resect as much thyroid tissue as possible without attempting resection of all adjacent structures because of the high incidence of postoperative morbidity (eg, vocal cord paralysis, esophageal fistula).

A greater extent of resection may be associated with slightly longer survival. For example, in a study of 55 patients with stage IVB or IVC ATC, Brignardello et al reported that maximal debulking—macroscopically complete resection (R0, R1), or R2 resection with minimal macroscopic residual tumor—followed by adjuvant therapy, can lengthen survival and improve quality of life by preventing airway compromise. [21]

In both stage IVB and IVC ATC, survival was 6.57 months with maximal debulking versus 3.25 months with partial debulking. Moreover, death secondary to local progression of tumor occurred in 21% of patients who had maximal debulking, compared with 69% of patients treated with partial debulking or no surgery.

See Thyroid Cancer Treatment Protocols for summarized information.

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Complications

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 of tracheal obstruction. [22]

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