While differentiated thyroid cancer is often an extremely curable cancer and, even when it is metastatic, a very slow growing cancer, anaplastic thyroid cancer is neither. Anaplastic thyroid cancer is one of the most aggressive and deadly cancers. All anaplastic thyroid cancers are considered to be Stage IV by the AJCC staging system. Fortunately, anaplastic thyroid cancer is rare (representing about one to two percent of all thyroid cancer).
This cancer will most often present as a rapidly growing neck mass in an elderly person. It is common for patients to present initially with hoarseness, dysphagia, dyspnea, and/or neck pain.
When a patient presents to a physician with this diagnosis, it is extremely important to confirm the diagnosis. Every year we will see several patients who have been referred for treatment of anaplastic thyroid cancer and have found the pathology diagnosis to be wrong. The most common mistake is that the diagnosis is made on a cytology specimen. We try to make sure pathology is obtained either with a core biopsy or, preferably, and incisional biopsy.
Other tumors that can be commonly mistaken for anaplastic thyroid cancer include differentiated thyroid cancer, medullary thyroid cancer, lymphoma, sarcoma, squamous cell cancers of the head and neck, and cancers that have metastasized from other part of the body to the thyroid.
At minimum we will check all tumors for thyroglobulin (almost always negative in cases of anaplastic thyroid cancer), TTF-1, CEA, calcitonin, and PAX8. In some cases, a definite diagnosis is not possible and a diagnosis will need to be made partly on the clinical situation.
Once it is confirmed that this is indeed anaplastic thyroid cancer, a baseline evaluation should be quickly done so that the initiation of treatment is not delayed. This includes an evaluation of the primary tumor (often done with a neck CT with contrast) as well as to see if there is any distant metastatic disease (this can be done with a CT scan of the chest, abdomen, and pelvis with contrast).
While a PET/CT scan can be done instead of a CT scan to evaluate for distant metastatic disease, it is important to get a good neck CT scan or MRI to determine if the mass is resectable. In addition, it is important to evaluate the person’s performance status and comorbidity. In all patients with anaplastic thyroid cancer, it important to start a discussion on advanced directives as early as possible.
In patients who have a poor performance status and/or significant comorbidity, especially if distant metastatic disease is present, it is very reasonable (and often advisable) to consider supportive care alone. Occasionally in this circumstance we have treated the patient with a cycle of hypofractionated radiation therapy (1480 cGy per fraction given twice a day for two consecutive days) to the neck mass just to help palliate the local symptoms followed by hospice care. The “quad shot” of radiation therapy can be repeated for two more cycles with each cycle about three weeks apart.
Due to the lack of good prospective clinical trials in this disease, management can vary at different centers. In all circumstances we will see if a clinical trial is available.
Because airway and esophageal compromise are a major concern, obtaining local control of this disease is crucial, and essential for patient quality of life, particularly in preventing asphyxiation and allowing maintenance of oral nutrition. We would recommend this approach even in many cases when distant metastatic disease is present.
While these tumors are rarely resectable, we do request a surgical consult from a skilled head and neck surgeon to evaluate for this possibility. Our practice is to treat patients with concurrent chemotherapy and radiation therapy to the neck immediately if surgery is not possible or as soon as possible after surgery is completed.
There are several reasonable chemotherapy regimens available using either single-agent or combination regiments. Reasonable chemotherapy agents include doxorubicin, cisplatin, and taxanes. Most often we will use doxorubicin 20 mg/m2 weekly during radiation therapy, although other regimens are also reasonable.
Radiation therapy planning needs to be done promptly. If Intensity-modulated radiation therapy (IMRT) is to be done, which we will often use, it might be reasonable to start with simple AP-PA radiation therapy for the first few fractions while IMRT is being planned to avoid any delay in initiating therapy.
Another option might be to start with chemotherapy while the radiation fields are being planned to try to maintain control of the disease. The disadvantage to this latter approach is the poor response of anaplastic thyroid cancer to chemotherapy.
The exception to our rule of first obtaining local control is if there is evidence that distant metastatic disease is growing rapidly. In this scenario, we will consider treating with chemotherapy alone.
Usually about two to four weeks after radiation therapy is finished, we will restage patients for evaluation of metastatic disease. If distant disease is present, it is important to have a frank discussion with the patient about management options, which should include best supportive care alone. There is no treatment that has been proven to improve either length or quality of life in this circumstance. If a patient does wish to try treatment, standard options would include either doxorubicin (+/- either cisplatin or carboplatin) or weekly paclitaxel (+/- either cisplatin or carboplatin).
While a number of tyrosine kinase inhibitors have shown good activity as single agents in differentiated thyroid cancer (e.g., sorafenib, pazopanib), so far their activity in anaplastic thyroid cancer has been disappointing. Since about 40 percent of anaplastic thyroid cancers will harbor a BRAF V600E mutation, this might be an attractive target and is currently being evaluated.
However, it is most likely that combination therapy will be required to have any efficacy in this aggressive and deadly cancer. Other mutations seen in anaplastic thyroid cancer with potential targeted therapy options include p53, RAS, PTEN, AKT, and PIK3CA. These tumors are very vascular as well as being associated with a high number of tumor-associated macrophages, both of which suggest potential ways to treat this disease in the future. At this time, almost everyone with distant metastatic anaplastic thyroid cancer will die within a year.
Follow Up If There Is No Evidence of Disease
In the cases when there is no distant metastatic disease present after the completion of radiation therapy, we will follow the patients closely for the first two to three years, usually at a three-month interval. After three years, the benefit of surveillance is even more questionable, and I would only recommend visits every six to 12 months with an endocrinologist who is comfortable with the treatment and surveillance for thyroid cancers.
There is no suggestion that further adjuvant therapy will benefit patients in this setting. Follow-up visits will include imaging of the neck and chest, exam, and blood work. We will often check a TSH and thyroglobulin. Although anaplastic thyroid cancers will not produce thyroglobulin, there may be a component of differentiated thyroid cancer present. It is not clear if the TSH needs to be suppressed as it does in differentiated thyroid cancer since it is unlikely it stimulated anaplastic thyroid cancer cells.
We often do it in case there is a differentiated thyroid cancer component; however, we have a low threshold to allow the TSH to drift into the low-normal range if there are potential concurrent medical issues to consider (e.g., atrial fibrillation).
If there is no evidence of disease after about six to 12 months, we would recommend treatment with radioactive iodine. While anaplastic thyroid cancer does not respond to radioactive iodine, it often presents as a transformation from a differentiated thyroid cancer and radioactive iodine can help control this.