Management of Patients with Anaplastic Thyroid Cancer
Publication Date: March 20, 2021
Last Updated: August 3, 2023
Diagnosis
Cytology, Histopathology, And Differential Diagnosis
Recommendation 1
FNA cytology can play an important diagnostic role in the initial evaluation of ATC, but parallel core biopsy may be necessary for definitive diagnosis and to obtain sufficient material for molecular interrogation. (S, L)
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Recommendation 2
Every effort should be made to establish a diagnosis via biopsy before proceeding with surgical resection, as surgical resection may be inappropriate. (S, L)
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Recommendation 3
Routine surgical pathology evaluation of resection specimens should focus on confirming a definitive diagnosis of ATC, documenting extent of disease, and defining the presence of any coexisting DTC and/or other pathologies. The proportion of tumor that represents ATC should also be documented. (S, L)
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Recommendation 4
Once ATC diagnosis is considered, assessment of BRAFV600E mutation should be expeditiously performed by IHC and confirmed/expeditiously assessed by molecular testing. (S, M)
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Recommendation 5
Molecular profiling should be performed at the time of ATC diagnosis to inform decisions related to the use of targeted therapies, especially as there are now FDA-approved mutation-specific therapies in this context. (S, M)
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Initial Evaluations
Recommendation 6
Initial radiological tumor staging should include cross-sectional imaging, in particular, CT neck, chest, abdomen, and pelvis with contrast (or MRI), and, if available, FDG PET/CT. Contrast-enhanced imaging of the brain (MRI preferred) should also be performed, if clinically indicated. (S, M)
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Good Practice Statement 1
In the event that biopsy of a suspected metastatic disease site is clinically indicated, primary management of ATC should not be delayed until biopsy is obtained. (GPS, )
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Good Practice Statement 2
All critical appointments and assessments that are required before primary treatment of ATC should be prioritized and completed as rapidly as possible. (GPS, )
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Recommendation 7
Every patient with ATC should undergo evaluation of the vocal cords at initial presentation, and thereafter based upon changing symptoms. (S, L)
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Treatment
Establishing Goals of Care
Recommendation 8
Comprehensive disease-specific multidisciplinary input should be attained before defining “goals of care” or undertaking therapeutic discussions with patients. Those involved in management decisions should include specialists highly experienced in treating ATC. (S, L)
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Good Practice Statement 3
Patients must have understanding and decision-making capacity to consent to treatment or to make particular medical decisions. Concerns about diminished or impaired capacity should prompt mental health and/or clinical ethics consultation to assess barriers to capacity. (GPS, )
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Good Practice Statement 4
Patients should be encouraged to draft both an advance directive in which they name a surrogate decision maker and list code status and other end-of-life preferences including POLST or MOST document. Circumstances where suspension of DNR may occur must be discussed with the patient as well. (GPS, )
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Good Practice Statement 5
A “goals-of-care” discussion should be initiated with the patient as soon as possible. In consultation with a multidisciplinary team, a candid session should be conducted in which there is full disclosure of the potential risks and benefits of various treatment options, updated frequently, including how such options will impact the patient’s life. Treatment options discussed should include all end-of-life options, such as hospice and palliative care. Patient preferences should guide clinical management. (GPS, )
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Recommendation 9
The treatment team should include palliative care expertise at every stage of patient management to help with pain and symptom control, as well as addressing psychosocial and spiritual issues. (S, L)
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Recommendation 10
The treatment team should engage hospice care for ATC patients who decline therapies against their tumor intending to prolong life, yet who still require symptom and pain relief spanning the remainder of their illness. (S, L)
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Recommendation 11
At all stages of palliative care and hospice care in ATC patients, practitioners should be aware of family systems, and how they affect patient decision-making. (S, L)
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Surgical Management of ATC
Recommendation 12
For patients with confined (stage IVA/IVB) ATC in whom R0/R1 resection is anticipated, we strongly recommend surgical resection.
- Value Statement: The authors for this recommendation placed a higher value for the benefit (longer overall survival) of surgical resection and placed a lower value for potential morbidity and subsequent delay in chemotherapy and/or radiation therapy.
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Recommendation 13
Radical resection (including laryngectomy, tracheal resections, esophageal resections, and/or major vascular or mediastinal resections) is generally not recommended given the poor prognosis of ATC and should be considered only very selectively after thorough discussion by the multidisciplinary team, also considered in light of new information based upon mutations present and the availability of targeted therapies. (S, L)
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Good Practice Statement 6
If surgery is undertaken, intraoperative frozen section and pathology consultation may be a helpful adjunct to inform surgical decision-making. (GPS, )
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Good Practice Statement 7
In patients without impending airway compromise, we advise against preemptive tracheostomy placement. (GPS, )
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Radiotherapy and Systemic Chemotherapy in Locoregionally-confined (Stages IVA and IVB) ATC: Principles and Approaches
Recommendation 14
Following R0 or R1 resection, the ATA recommends that good performance status patients with no evidence of metastatic disease who wish an aggressive approach should be offered standard fractionation IMRT with concurrent systemic therapy. (S, L)
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Good Practice Statement 8
Radiation therapy should begin no later than 6 weeks after surgery. (, )
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Good Practice Statement 9
Patient goals of care, medical and psychosocial fitness for therapy, potential toxicities, financial considerations, and robustness of social support must be prominently considered in the decision to proceed with aggressive multimodal therapy. (, )
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Good Practice Statement 10
Cytotoxic chemotherapy can be initiated within 1 week of surgery, providing sufficient healing, in anticipation of subsequent chemoradiation. (, )
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Recommendation 15
The ATA recommends that patients who have undergone R2 resection or have unresectable but nonmetastatic disease with good performance status and who wish an aggressive approach be offered standard fractionation IMRT with systemic therapy. Alternatively, in BRAFV600E-mutated ATC, combined BRAF/MEK inhibitors can be considered in this context. (S, L)
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Recommendation 16
In patients with unresectable disease during initial evaluation in whom radiotherapy and/or systemic (chemotherapy or combined BRAF/MEK inhibitors) therapy render the tumor potentially resectable, the ATA recommends reconsideration of surgical resection. (S, L)
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Good Practice Statement 11
In patients of poor performance status, palliative or preventative (no residual disease present) locoregional radiotherapy over high dose radiotherapy is suggested. (GPS, )
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Recommendation 17
Among patients who are to receive radiotherapy for unresectable thyroid cancer or in the postoperative setting, IMRT is recommended. (S, L)
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Recommendation 18
The use of cytotoxic chemotherapy involving a taxane (paclitaxel or docetaxel), administered with or without anthracyclines (doxorubicin) or platin (cisplatin or carboplatin), is recommended in patients treated with definitive-intention radiation. (S, L)
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Systemic Therapeutic Approaches to Locally Advanced Unresectable and/or Metastatic Disease
Recommendation 19
Among ATC patients with unresectable or advanced disease wishing aggressive therapy, the ATA suggests early initiation of cytotoxic chemotherapy as an initial and potentially bridging approach until mutational interrogation results and/or mutationally specified therapies might be available, and if appropriate. (C, L)
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Recommendation 20
In BRAFV600E-mutated IVC and in unresectable IVB ATC patients who decline radiation therapy, initiation of BRAF/MEK inhibitors (dabrafenib plus trametinib) is recommended over other systemic therapies if available. (S, L)
- Value Statement: The authors—including patient advocates—for this recommendation placed a high value on available and emerging data indicating the potential for profound benefit from using this approach in a setting where little hope had previously existed, supporting the strong recommendation made in the presence of low-quality evidence.
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Recommendation 21
In BRAFV600E-mutated unresectable stage IVB ATC in which radiation therapy is feasible, chemoradiotherapy or neoadjuvant dabrafenib/trametinib represents alternatives to initial therapy. (C, L)
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Recommendation 22
In BRAF non-mutated patients, radiation therapy with concurrent chemotherapy should be considered in an effort to maintain the airway in patients with low burden of metastatic disease. (S, L)
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Recommendation 23
In NTRK or RET fusion ATC patients with stage IVC disease, the ATA suggests initiation of a TRK inhibitor (either larotrectinib or entrectinib) or RET inhibitor (either selpercatinib or pralsetinib), preferably in a clinical trial, if available. (C, VL)
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Recommendation 24
In IVC ATC patients with high PD-L1 expression, checkpoint (PD-L1, PD1) inhibitors can be considered first-line therapy in the absence of other targetable alterations or as later line therapy, preferably in the context of a clinical trial. (C, L)
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Good Practice Statement 12
Patients with BRAF wild-type (BRAF “negative” or unknown mutation status) IVB unresectable or metastatic ATC wishing an aggressive approach and not receiving chemoradiation should be encouraged to participate in clinical trials given the rarity of ATC, the paucity of data in support of improved survival or quality of life from any systemic therapeutics, and the need to develop evidence-based safe and effective therapeutic approaches in advanced ATC. (GPS, )
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Recommendation 25
In metastatic ATC patients lacking other therapeutic options including clinical trials, the ATA suggests cytotoxic chemotherapy including a taxane and/or an anthracycline or taxane with or without cis- or carbo-platin. (C, L)
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Good Practice Statement 13
Therapeutic decision-making in the setting of PD after initial therapy regardless of somatic mutational status or therapy is very complex and not easily defined by an algorithmic approach. In this setting, care guided by an expert in ATC therapeutics is best pursued. (GPS, )
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Good Practice Statement 14
Since prognosis is dire in metastatic and progressive ATC, best supportive care (hospice) should also be discussed as an option. (GPS, )
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Recommendation 26
In ATC patients considering therapy, the ATA recommends brain MRI assessing the presence of brain metastases at time of diagnosis as a part of initial staging and when symptoms otherwise prompt concern. (S, L)
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Recommendation 27
In ATC patients with neurologic brain compressive symptoms or signs, the ATA recommends dexamethasone (4–16 mg/day). (S, L)
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Recommendation 28
In ATC patients with brain metastases referral to neurosurgery/radiation oncology should be made. (S, L)
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Good Practice Statement 15
Patients with brain metastases may be expected to be at increased risk if operating motor vehicles or if placed in a situation in which they may jeopardize themselves or others and therefore should be appropriately counseled. (GPS, )
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Approaches to Bone Metastases
Recommendation 29
In patients with ATC with symptomatic or threatening bone metastases—but without structural compromise or threatened spinal cord compression in need of surgical remediation—the ATA recommends palliative radiotherapy. (S, L)
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Recommendation 30
In patients with ATC with bone metastasis causing structural compromise in a weight-bearing region or threatening spinal cord compression, the ATA recommends orthopedic fixation before initiation of palliative radiotherapy. (S, L)
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Recommendation 31
In patients with ATC with bone metastasis, the ATA suggests periodic intravenous bisphosphonate infusions or subcutaneous RANK ligand inhibitor. (C, L)
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Good Practice Statement 16
In patients on systemic therapy who develop oligo-progressive disease, local tumor-directed therapy may be considered to postpone the need to change otherwise beneficial systemic therapy. (GPS, )
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Approaches to Other Sites of Metastases
Systemic therapy as described above is the first line of treatment, but if a particular metastasis is symptomatic or has progressed despite systemic therapy, treatment may be individualized to metastatic locations, much as would be the case for other malignancies (N) (, )
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Approaches to Oligoprogressive Metastatic Disease
Good Practice Statement 16
In patients on systemic therapy who develop oligo-progressive disease, local tumor-directed therapy may be considered to postpone the need to change otherwise beneficial systemic therapy. (GPS, )
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Recommendation Grading
Overview
Title
Management of Patients with Anaplastic Thyroid Cancer
Authoring Organization
American Thyroid Association
Publication Month/Year
March 20, 2021
Last Updated Month/Year
October 11, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Update_in_progress
Country of Publication
US
Document Objectives
Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC.
Target Patient Population
Patients with anaplastic thyroid cancer (ATC)
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory, Hospital, Outpatient, Radiology services
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Counseling, Diagnosis, Assessment and screening, Treatment, Management
Diseases/Conditions (MeSH)
D065646 - Thyroid Carcinoma, Anaplastic
Keywords
anaplastic thyroid cancer
Source Citation
Bible KC, Kebebew E, Brierley J, Brito JP, Cabanillas ME, Clark TJ Jr, Di Cristofano A, Foote R, Giordano T, Kasperbauer J, Newbold K, Nikiforov YE, Randolph G, Rosenthal MS, Sawka AM, Shah M, Shaha A, Smallridge R, Wong-Clark CK. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2021 Mar;31(3):337-386. doi: 10.1089/thy.2020.0944. Erratum in: Thyroid. 2021 Oct;31(10):1606-1607. PMID: 33728999; PMCID: PMC8349723.
Methodology
Number of Source Documents
330
Literature Search Start Date
February 15, 2017
Literature Search End Date
May 11, 2020