Anaplastic Thyroid Cancer

Background

• Anaplastic thyroid cancer is the least common and the most lethal form of thyroid cancer, accounting for 1%-2% of all thyroid cancers, but 20%-50% of thyroid cancer deaths in the United States.
• Anaplastic thyroid cancer can arise de novo or as progression of differentiated thyroid cancer.
• Common clinical presentations of anaplastic thyroid cancer include rapidly enlarging thyroid mass and signs and symptoms associated with tumor-induced mechanical compression or tumor invasion of adjacent structures (such as frank stridor, dyspnea, hoarse voice, and dysphagia).
• All patients with anaplastic thyroid cancer are classified as stage IV. Due to the aggressive nature of anaplastic thyroid cancer, mortality is almost universal with death typically occurring within 3-6 months of diagnosis.

Evaluation

• Initial testing for patients with suspected anaplastic thyroid cancer
  • Perform a biopsy of the neck mass.
    • Fine needle aspiration (FNA) biopsy for cytology is typically the initial first attempt of biopsy in patients with suspected anaplastic thyroid cancer.
    • If cellular yield from FNA biopsy is insufficient, core biopsy may be diagnostic.
  • Perform a pathological evaluation, including an assessment of immunohistochemical markers. BRAF V600E mutation should be expeditiously assessed with immunohistochemistry (Strong recommendation).
• Testing after diagnosis of anaplastic thyroid cancer
  • Perform molecular testing at time of diagnosis to help guide management decisions in terms of genetically informed targeted therapies (Strong recommendation). Molecular testing should include confirmation of BRAF V600E mutation (Strong recommendation).
  • Perform blood tests, including
    • complete blood count with differential
    • chemistry panel, including
      • electrolytes
      • blood urea nitrogen (BUN) and creatinine
      • glucose
      • liver function tests
    • calcium and phosphorus
    • thyroid function tests (thyroid-stimulating hormone and free thyroxine)
    • thyroglobulin
  • Imaging tests should be performed for initial radiological tumor staging.
    • Cross-sectional imaging should include:
      • computed tomography (CT) with contrast (or magnetic resonance imaging [MRI] using gadolinium contrast) of the neck, chest, abdomen, and pelvis (Strong recommendation)
      • ¹⁸fluorodeoxyglucose-positron emission tomography (FDG-PET) fused to coincident computed tomography scan of whole body (if available) (Strong recommendation)
    • Perform MRI of the brain to assess for presence of brain metastases (Strong recommendation).
  • Perform a vocal cord evaluation at initial presentation to assess vocal cord mobility (Strong recommendation), preferably with a laryngeal evaluation using fiberoptic laryngoscopy.

Management

• Initiate management goals discussion with patient and multidisciplinary team as early as possible.
• Palliative care expertise should be included at all stages of management to provide pain and symptom control and to address psychosocial and spiritual issues (Strong recommendation).
• Approach to stage IVA or resectable stage IVB anaplastic thyroid cancer:
  • Surgical resection is recommended if R0 or R1 resection is anticipated in patients with stage IVA or stage IVB anaplastic thyroid cancer (Strong recommendation).
  • In patients with good performance status and no metastatic disease after R0 or R1 resection who desire aggressive therapy:
    • Offer standard fractionation intensity-modulated radiation therapy (IMRT) with concurrent systemic chemotherapy (Strong recommendation).
    • Following R0 or R1 resection, systemic chemotherapy can begin as soon as patient is sufficiently recovered from surgery (even within 1 week of surgery) in anticipation of subsequent chemoradiation therapy.
    • Give cytotoxic chemotherapy involving a taxane (docetaxel or paclitaxel) given with or without anthracyclines (doxorubicin) or platin (carboplatin or cisplatin) (Strong recommendation).
    • Begin radiation therapy within 6 weeks of surgery after postoperative healing has occurred and patient is able to lie supine and tolerate immobilization.
  • Elect best supportive or hospice care at any point, if warranted.
• Approach to unresectable stage IVB anaplastic thyroid cancer:
  • If patient desires aggressive therapy, consider initiating cytotoxic chemotherapy as the initial therapy and potentially bridging approach until molecular testing results and/or therapies become available (if appropriate) (Weak recommendation).
  • Genetically informed targeted therapy may be an alternative initial option.
    • In patients with BRAF V600E-mutated unresectable IVB anaplastic thyroid cancer:
      • if radiation is feasible, consider neoadjuvant chemoradiation therapy as an initial therapy (Weak recommendation)
      • if patient with BRAF V600E-mutated unresectable stage IVB anaplastic thyroid cancer declines radiation therapy or radiation therapy is not feasible, initiate therapy with combined BRAF/MEK inhibitors (dabrafenib plus trametinib) (Strong recommendation)
    • If patient with unresectable stage IVB anaplastic thyroid cancer does not have BRAF V600E mutation, consider other targeted therapy based on tumor genetics (such as RETor NTRK fusions).
  • If previously unresectable tumor becomes potentially resectable after radiation therapy and/or systemic therapy (chemotherapy or combined BRAF/MEK inhibitors), reconsider surgical resection (Strong recommendation).
  • Elect best supportive or hospice care at any point, if warranted.
• Approach to stage IVC anaplastic thyroid cancer:
  • For patients who do not desire aggressive care, consider best supportive care or hospice.
  • For patients who desire aggressive care:
    • Consider initiating cytotoxic chemotherapy as initial therapy and potentially bridging approach until molecular testing results and/or therapies become available (if appropriate) (Weak recommendation).
    • Consider cytotoxic chemotherapy (including taxane and/or anthracycline or taxane with or without cisplatin or carboplatin) in patients with metastatic anaplastic thyroid cancer who lack other therapeutic options, including clinical trials (Weak recommendation).
    • Genetically informed targeted therapy may be an alternative option.
      • If patient has BRAF V600E-mutated stage IVC anaplastic thyroid cancer, initiate therapy with combined BRAF/MEK inhibitors (dabrafenib plus trametinib) (Strong recommendation).
      • If patient does not have BRAF V600E-mutated stage IVC anaplastic thyroid cancer, consider other tumor genetics.
        • In patients with stage IVC disease and RET or NTRK fusion, consider inhibitors targeting the respective fusion, preferably in the setting of clinical trials, if available (Weak recommendation).
        • In patients with stage IVC anaplastic thyroid cancer and high programmed cell death ligand-1 (PD-L1) expression, consider PD-L1 or programmed cell death protein-1 (PD-1) checkpoint inhibitors as initial (if no other targetable alterations) or later therapy, preferably in setting of clinical trial (Weak recommendation).