Recurrence

Locoregional recurrence means thyroid cancer that has persisted or recurred in the ‘thyroid bed’ where the thyroid used to be (‘locally’ in the central neck compartment) or anywhere nearby in the neck (‘regionally’ in the lateral neck compartment) – in both cases this would mean cancer that has spread to a lymph node(s) in the neck.

Distant metastatic disease means thyroid cancer that has spread distantly away from the neck (e.g. lungs, bone, liver, brain, etc.).

Image Source: Mary Ann Liebert, Inc.

If the cancer is grossly visible on imaging and/or objectively proven on biopsy, surgery to remove the cancer is the preferred treatment option.

• If it can be tolerated by the patient based on age and other medical problems.
• And the surgery is not too morbid (e.g. total laryngectomy, pharyngectomy / esophagectomy, carotid artery resection, etc.).

Radioactive Iodine (RAI) is unlikely to be effective in patients who have grossly visible cancer on imaging.

• Also, if previously given, the relatively low risks from a single dose of RAI can become much greater due to cumulative radiation effects from multiple doses.
• Cure rates for locoregional WDTC recurrence can still be quite high, especially if surgery can be performed and it is recognized early on during surveillance.
• Sometimes the locoregional recurrence can always be measured in the blood with elevated thyroglobulin levels but never identified on imaging.
  • In these cases, the recurrent cancer behaves like a chronic disease, always present but not behaving aggressively.
  • Surveillance in this scenario would be indefinite.
• Rarely can locoregional WDTC recurrence accumulate additional DNA alterations (mutations, rearrangements, etc.) and start to behave more aggressively and/or life-threatening.
• Locoregional recurrences that are considered unresectable based on aggressive invasion into critical structures of the neck, or resection would cause unacceptable morbidity to the patient, neo-adjuvant (medical treatment given prior to surgery) with TKI (tyrosine kinase inhibitors) and/or targeted molecular therapy (requires prior molecular analysis / gene sequencing and the existence of a therapy targeting the identified DNA alteration) can be considered with the goal to shrink the cancer to a point where it could be resected with acceptable morbidity.
  • To explore these treatment options as a patient, you should be seen by a Head & Neck Cancer Oncologist who specializes in the treatment of advanced thyroid cancers (typically practicing at an academic university hospital).
• Traditional radiation (e.g., External Beam Radiation) can also be considered for unresectable locoregional recurrence with a palliative (non-curative) goal to prevent progressive growth or invasion into nearby structures.
  • To explore these treatment options as a patient, you should be seen by a Head & Neck Cancer Radiation Oncologist who specializes in the treatment of advanced thyroid cancers (typically practicing at an academic university hospital).

~5% of all thyroid cancer patients (not just WDTC’s) have distant metastatic cancer discovered either at the time of cancer diagnosis or during surveillance.

Once the cancer has spread to a distant site, it is no longer curable.

• Prognosis, treatment options, and survival rates vary widely based on the type of cancer, driving DNA alteration, its ability to respond to RAI, and the site of metastasis.

Important to obtain gene sequencing and/or molecular analysis of the tumor cells to identify the DNA alteration driving the cancer.

• The DNA alteration causing the cancer can predict the most common site for distant spread.
  • BRAF mutations (PTC) spread via the lymphatic system and are most likely to spread to the lung after the neck.
  • RAS mutations (FTC and OCA) spread hematogenously (through the blood system) and metastasis to bone are more common.
• The identified DNA alteration can also help predict response to RAI.
  • RAS mutations are more likely to have a favorable response to RAI.
• Assists in identification of targeted molecular therapies for systemic (whole body) treatment.

Site of distant metastasis determines overall survival.

• Lung only – 5-year survival is 77%.
• Bone – 5-year survival is 25%
• Liver – 5-year survival is 21%.

Treatment options

• Surgical resection of a localized site of recurrence if possible is preferred if not too morbid (unfortunately this is often not possible).
• RAI can be considered for palliative (non-curative) treatment.
  • Depends on the cancer cell’s ability to absorb iodine.
    • Can be assessed with a whole-body iodine scan using I-123.
  • Dependent on driving DNA alteration.
    • BRAF less responsive to RAI.
    • RAS typically more responsive to RAI.
  • Balance cumulative effects of radiation from multiple doses vs expected effect of treatment.
• Focal external beam radiation to an isolated site of disease is favored over systemic therapy.
• Systemic therapy
  • Medication given that reaches the entire body.
    • Two classes
      • Multikinase inhibitors that target growth and division of thyroid cancer cells regardless of the driving DNA alteration.
      • Targeted molecular therapies based on an identified DNA alteration causing the cancer.
  • Most distant disease is indolent (slow growing) and there is not an immediate need to start systemic therapy.
  • Criteria for starting systemic therapy include visible growth of disease on imaging, doubling time of the tumor marker (e.g. Thyroglobulin) measured in the blood, symptomatic disease, or compromised organ function.
  • 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 & Neck Cancer 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.