Anaplastic thyroid cancer
Encyclopedia
Anaplastic thyroid cancer (ATC) is a form of thyroid cancer
which has a very poor prognosis (14% ten-year survival rate) due to its aggressive behavior and resistance to cancer treatments.
). The presence of regional lymphadenopathy
in older patients in whom needle aspiration biopsy
reveals characteristic vesicular appearance of the nuclei would support a diagnosis of anaplastic carcinoma.
Treatment of anaplastic-type carcinoma is generally palliative in its intent for a disease that is rarely cured and almost always fatal, with worse prognosis associated with large tumours, distant metastases, acute obstructive symptoms, and leukocytosis
. Death is attributable to upper airway obstruction and suffocation in half of patients, and to a combination of complications of local and distant disease, or therapy, or both in the remainder.
Anaplastic thyroid cancer is extremely aggressive; in most cases death occurs in less than 1 year as a result of aggressive local growth and compromise of vital structures in the neck. ATC in most series has a median survival of 4 to 5 months from the time of diagnosis, with rare long-term survivors.
Palliative treatment consists of radiation therapy
usually combined with chemotherapy
.
However, with today's technology, new drugs, such as combretastatin
(fosbretabulin), bortezomib
and TNF-Related Apoptosis Induced Ligand (TRAIL), are being introduced and trialed in clinical labs and human clinical studies. Based on encouraging Phase I and II clinical trial results, with combretastatin (fosbretabulin), a type of drug that selectively destroys tumor blood vessels, a large, multi-national clinical trial is being undertaken to determine whether the drug can extend the survival of patients with ATC. Recent studies in Italy have shown positive results against ATC, but more tests outside the lab are needed to confirm this before it can be used in chemotherapy. There have been some case studies where patients with aggressive thyroid cancer have survived outside the mean expected survival time.
(EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended.
The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomised controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine-avid cancer.
Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non-treatment groups in the use of radio-iodine and post-treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies.
Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small.
Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first-line treatment.
There are a number of clinical trials for anaplastic thyroid carcinoma underway or being planned.
Thyroid cancer
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm , such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected...
which has a very poor prognosis (14% ten-year survival rate) due to its aggressive behavior and resistance to cancer treatments.
Presentation
Anaplastic tumors have a high miotic rate and lymphovascular invasion. It rapidly invades surrounding tissues (such as the tracheaVertebrate trachea
In tetrapod anatomy the trachea, or windpipe, is a tube that connects the pharynx or larynx to the lungs, allowing the passage of air. It is lined with pseudostratified ciliated columnar epithelium cells with goblet cells that produce mucus...
). The presence of regional lymphadenopathy
Lymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
in older patients in whom needle aspiration biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
reveals characteristic vesicular appearance of the nuclei would support a diagnosis of anaplastic carcinoma.
Prognosis
The overall 5-year survival rate of anaplastic thyroid cancer has been given as 7% or 14%, although the latter has been criticized as being overestimated.Treatment of anaplastic-type carcinoma is generally palliative in its intent for a disease that is rarely cured and almost always fatal, with worse prognosis associated with large tumours, distant metastases, acute obstructive symptoms, and leukocytosis
Leukocytosis
Leukocytosis is a raised white blood cell count above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, and is observed in certain parasitic infections...
. Death is attributable to upper airway obstruction and suffocation in half of patients, and to a combination of complications of local and distant disease, or therapy, or both in the remainder.
Anaplastic thyroid cancer is extremely aggressive; in most cases death occurs in less than 1 year as a result of aggressive local growth and compromise of vital structures in the neck. ATC in most series has a median survival of 4 to 5 months from the time of diagnosis, with rare long-term survivors.
Treatment
Unlike its differentiated counterparts, anaplastic thyroid cancer is highly unlikely to be curable either by surgery or by any other treatment modality, and is in fact usually unresectable due to its high propensity for invading surrounding tissues.Palliative treatment consists of radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
usually combined with chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
.
However, with today's technology, new drugs, such as combretastatin
Combretastatin
The combretastatins are a class of natural stilbenoid natural phenols. A variety of different natural combretastatin molecules are present in the bark of Combretum caffrum, commonly known as South African Bush Willow...
(fosbretabulin), bortezomib
Bortezomib
Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma...
and TNF-Related Apoptosis Induced Ligand (TRAIL), are being introduced and trialed in clinical labs and human clinical studies. Based on encouraging Phase I and II clinical trial results, with combretastatin (fosbretabulin), a type of drug that selectively destroys tumor blood vessels, a large, multi-national clinical trial is being undertaken to determine whether the drug can extend the survival of patients with ATC. Recent studies in Italy have shown positive results against ATC, but more tests outside the lab are needed to confirm this before it can be used in chemotherapy. There have been some case studies where patients with aggressive thyroid cancer have survived outside the mean expected survival time.
Post-operative radiotherapy
The role of external beam radiotherapyExternal beam radiotherapy
External beam radiotherapy or teletherapy is the most common form of radiotherapy. The patient sits or lies on a couch and an external source of radiation is pointed at a particular part of the body...
(EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended.
The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomised controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine-avid cancer.
Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non-treatment groups in the use of radio-iodine and post-treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies.
Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small.
Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first-line treatment.
Adjuvant therapy
In the absence of extracervical or unresectable disease, surgical excision should be followed by adjuvant radiotherapy. In the 18–24% of patients whose tumour seems both confined to the neck and grossly resectable, complete surgical resection followed by adjuvant radiotherapy and chemotherapy could yield a 75–80% survival at 2 years.There are a number of clinical trials for anaplastic thyroid carcinoma underway or being planned.