Anaplastic Thyroid Carcinoma

Biopsy (FNA) of a palpable thyroid mass (typically rapidly growing) or incidental thyroid mass noted on imaging for work up of changes in voice, breathing, or swallowing.

• Diagnosis by FNA can at times be challenging, sometimes requiring a core needle biopsy (different type of biopsy using a larger needle to obtain more cells).
  • If high clinical suspicion for ATC based on presentation and/or appearance on imaging, low threshold to send pathology slides to a tertiary or academic medical center for rapid second opinion.
• If biopsy is confirmed on FNA, rapid BRAF V600e mutational testing should be performed on the cells (PCR; polymerase chain reaction or IHC; immunohistochemical staining).
  • The presence of this mutation can affect initial and subsequent treatment strategies (see below under Treatment).

Imaging

• If not already obtained, CT of the Neck and Chest with Contrast.
  • Essential to determine if the cancer can be removed with surgery.
    • Often the cancer has grossly invaded critical structures of the neck (larynx, trachea, pharynx, esophagus, carotid artery, spine) that can make surgical removal impossible or too morbid.
• Whole Body PET Scan
  • One of the few thyroid cancers that is reliably visible on PET scan.
  • Will help to determine if there is any distant spread of the cancer.
• MRI of the Brain with contrast.
  • Rule out spread to the brain (PET scans are not good at ruling out spread of cancers to the brain).

Examination of the vocal cords with flexible fiberoptic camera to ensure no compromised function prior to surgery.

• If there is suspicion that the cancer is affecting the recurrent laryngeal nerve (controls movement of the vocal cords and voice) based on symptoms, imaging, and/or fiberoptic camera exam, there is an increased likelihood that the nerve will need to be sacrificed (cut in order to remove all the cancer) during the surgery.

If the cancer is considered resectable based on careful evaluation of imaging, then surgery is the preferred initial treatment strategy.

• Low threshold to perform tracheoscopy / bronchoscopy and esophagoscopy on day of surgery to ensure cancer remains resectable (no invasion into larynx / trachea and esophagus, respectively).
• Low threshold to perform concurrent central and/or lateral neck dissections for biopsy proven or highly suspicious lymph nodes on imaging.
• Surgery should be performed ASAP by an experienced surgeon.
  • For all types of thyroid cancer, surgical outcomes / cure rates are the highest and complication rates are the lowest when surgery is performed by a high-volume surgeon (> 50 thyroidectomy surgery per year).
• Surgery when resectable is still indicated if distant metastases are appreciated on imaging.
  • Will prevent the severe morbidity of potential future invasion into the larynx, trachea, esophagus, and carotid artery.
  • Allows for any adjuvant therapy (treatment given after surgery) to be more effective.
• If the cancer is deemed to be unresectable, but there is a + BRAF V600E mutation present on biopsy, neoadjuvant (therapy given prior to surgery) treatment with dabrafenib + trametinib systemic therapy can be considered.
  • Should be administered by a Head and Neck Cancer Oncologist at a high volume Academic Medical Center, typically as part of a clinical trial.
  • Imaging is repeated following completion of neoadjuvant treatment to determine if the cancer is resectable.
    • If resectable, proceed with surgery as above.
    • If unresectable, consider external beam radiation (EBRT) with / without chemotherapy based on available clinical trials.
• If the cancer is considered unresectable and BRAF V600E negative on biopsy, consider external beam radiation (EBRT) with / without chemotherapy based on available clinical trials.
  • Unresectable cancer should never be ‘debulked’ or just partially removed.
• If at any time the cancer is considered unresectable, patient / family / treatment team should collectively consider:
  • Palliate tracheotomy to prevent future airway compromise (cancer directly invading the larynx and/or trachea effecting the patient’s ability to breathe).
  • Feeding tube placement to allow for adequate nutrition and administration of medications if the cancer invades the pharynx or esophagus.
  • Establish goals of treatment and advance directives / end of life care plan.

Following surgery for resectable cancer, External Beam Radiation (EBRT) to the neck with or without systemic chemotherapy with goal to:

• Kill off any potential residual cancer cells.
• Decrease chances of future recurrence.
  • Typically administered by a multidisciplinary Head and Neck Cancer Radiation Oncology team at a high volume Academic Medical Center, as part of an ongoing clinical trial.

Pathology specimen should be sent for gene sequencing and/or molecular analysis to identify possible targeted systemic therapies.

Radioactive Iodine (RAI) is not indicated given that the thyroid cells no longer possess the ability absorb iodine.

All ATC’s are considered Stage IV by the AJCC reflecting the poor prognosis.

• Stage IVA:
  • Cancer confined to the thyroid with no spread to the regional lymph nodes in the neck, or distantly beyond the neck.
• Stage IVB:
  • Cancer has spread to a regional lymph node in the neck, but not distantly beyond the neck.
  • Cancer has grossly invaded the strap muscles of the neck, but not distantly beyond the neck.
  • Cancer has grossly invaded larger structures of the neck (larynx, trachea, esophagus, recurrent laryngeal nerve, carotid artery, spine, etc.), but has not distantly beyond the neck.
• Stage IVC:
  • The cancer has spread distantly beyond the neck.

Prognosis

• Based on staging of the cancer, prognosis can be predicted with 5 year expected survival rates.
• How many patients will not die from their thyroid cancer 5 years following treatment?
  • Stage IVA
    • 39%
  • Stage IVB
    • 11%
  • Stage IVC
    • 4%
• Prognosis has been improving in recent years (not yet reflected in the above 5-year survival rates) due to:
  • Introduction of neoadjuvant treatment which can make some previously unresectable cancers resectable.
  • Increasing number of targeted systemic therapies now available extending life even when distant spread is present.

Predominantly Imaging:

• CT of the Neck with contrast and Whole-Body PET scans every 3 months.
• MRI of the Brain with contrast every year.
• Consider less frequent imaging if no evidence of disease or stable disease over a continued period.

No tumor markers exist to measure in the blood for ATC.

Recurrence in the neck should be treated surgically if possible.

• If not possible, but +BRAF V600E, and not already administered, consider the role for neoadjuvant treatment with dabrafenib + trametinib systemic therapy to see if the cancer shrinks to become resectable.
• Surgery following EBRT can be very challenging due to increased scar tissue and inflammation, with accordingly higher completion rates which should be considered.

Distant Metastases

• Once ATC has spread beyond the neck, cure is no longer possible.
  • Treatment should be focused on extending life, preserving quality of life, and/or palliation.
• Surgical resection of a focal distant metastasis if possible is preferred if not too morbid (unfortunately this is not often possible).
• Focal external beam radiation to a focal site of disease can be considered if possible.
• Gene sequencing and/or molecular analysis should be performed to identify any possible targets for systemic therapies.
  • Systemic therapy
    • These treatments are not curative, and their side effects can limit their use in some patients.
• To explore these treatment options as a patient, you should be seen by a Head and Neck Oncologist who specializes in the treatment of advanced thyroid cancers (typically practicing at an academic university hospital).

If at any time the cancer is considered not curable, the patient / family / treatment team should collectively consider:

• Palliate tracheotomy to prevent future airway compromise (cancer directly invading the larynx and/or trachea effecting the patient’s ability to breathe).
• Feeding tube placement to allow for adequate nutrition and administration of medications if the cancer invades the pharynx or esophagus.
• Establish goals of treatment and advance directives / end of life care plan.