What is the best treatment for anaplastic thyroid cancer?

Treatment of Anaplastic Thyroid Cancer

For patients with locally resectable anaplastic thyroid cancer, multimodality therapy combining hyperfractionated external beam radiation with doxorubicin-based chemotherapy, followed by surgery in responders, offers the best chance for survival and local disease control. 1

Treatment Algorithm by Disease Stage

Locally Resectable Disease (Stage IVA-IVB)

Multimodality therapy is the standard approach:

• Initiate hyperfractionated external beam radiation therapy (EBRT) combined with radiosensitizing doses of doxorubicin, which achieves approximately 80% local response rates with median survival of 1 year 1
• Perform surgical resection to gross negative margins in patients who respond to chemoradiation, as this represents the only curative opportunity 1
• Use intensity-modulated radiation therapy (IMRT) when available to reduce toxicity while maintaining efficacy 1
• Consider docetaxel/doxorubicin combination regimens as an alternative, which can be administered with or without radiation therapy per American Thyroid Association guidelines 1

Important caveat: The NCCN panel acknowledges that considerable toxicity accompanies hyperfractionated EBRT combined with chemotherapy, and prolonged remission remains uncommon despite optimal results 1

Unresectable or Metastatic Disease (Stage IVC)

Chemotherapy alone is the primary treatment option:

• Single-agent doxorubicin is the only FDA-approved agent for anaplastic thyroid cancer and should be considered first-line 1
• Single-agent paclitaxel at 60-90 mg/m² intravenously weekly may benefit newly diagnosed patients, particularly those with stage IVB disease, with reported survival improvements 1
• Carboplatin/paclitaxel combinations can be considered, though the FACT trial showed only nonsignificant survival benefit (5.2 vs 4.0 months median survival) 1
• Aggressive palliative radiotherapy (50 Gy to gross tumor) for metastatic disease with good performance status achieves median survival of 6 months 2

Critical note: Single-agent cisplatin is NOT recommended for advanced/metastatic anaplastic thyroid cancer or patients with impaired renal function 1

Concurrent Chemoradiation Considerations

When using concurrent chemoradiation:

• Administer weekly chemotherapy regimens rather than higher-dose schedules, as recommended by American Thyroid Association guidelines 1
• Recognize that chemoradiation is generally more toxic than chemotherapy alone, requiring careful patient selection 1
• Higher doses of chemotherapeutic drugs have NOT improved control of distant disease or survival 1

Clinical Trial Enrollment

All patients—regardless of surgical resection status—should be considered for clinical trials given the poor outcomes with standard therapy. 1

Investigational approaches include:

• Vascular disrupting agents (fosbretabulin, combretastatin A4 phosphate, crolibulin) 1
• BRAF/MEK inhibitor combinations (dabrafenib/trametinib) for BRAF V600E mutated tumors, which received FDA approval 3
• Multi-targeted tyrosine kinase inhibitors (sorafenib, lenvatinib, sunitinib) 1, 4, 3
• Immunotherapy with anti-PD-1/PD-L1 agents (pembrolizumab), particularly when combined with BRAF inhibitors 3

Palliative and Supportive Care

Early initiation of palliative care is paramount given the universally poor prognosis:

• Initiate end-of-life care discussions at diagnosis to establish clear understanding of airway management preferences 1
• Consider EBRT/IMRT for palliation to prevent asphyxiation and improve local control 1
• Recognize that tracheostomy is often morbid and temporary, and may not align with patient preferences 1
• Provide enteral nutrition support for patients with dysphagia, following careful discussion of patient wishes 1

Surgical Considerations

Surgery alone is NOT curative except in rare cases:

• Total thyroidectomy with attempted complete tumor resection has not shown survival benefit except for patients with small tumors entirely confined to the thyroid 1
• Experienced surgeons are essential for evaluating disease extent in the larynx, trachea, and neck before attempting resection 1
• Administer levothyroxine if total thyroidectomy is performed 1

Radiation Therapy for Metastatic Disease

For isolated metastases:

• Surgical excision or external irradiation should be considered for isolated skeletal metastases 1
• Neurosurgical resection, radiation therapy, or both are recommended for solitary brain lesions, though median survival after brain metastases diagnosis is only 1.3 months 1

Evidence Quality and Prognosis Context

The NCCN guidelines classify these recommendations as Category 2A (uniform consensus based on lower-level evidence), reflecting the rarity of this disease and difficulty conducting high-quality trials 1. Median survival remains 3-6 months despite treatment 5, 2, though aggressive multimodal approaches in selected patients have achieved survival beyond 3 years 2, 4.

Targeted therapies outside clinical trials are NOT currently recommended for anaplastic thyroid cancer, despite their use in other thyroid cancer subtypes 1.