Anaplastic Thyroid Cancer
Key Background
Key Background
- ATC patients have a historical median survival of about 5 months and a 1-year overall survival of 20%.
Table 1. Key Steps in the Management of Anaplastic Thyroid Cancer
- Rapidly and definitively establish the diagnosis
Because ATC is a highly dedifferentiated cancer that retains few characteristics of noncancerous thyroid cells, attaining a definitive diagnosis can be challenging, yet critical. Time is also of the essence because of the very rapid growth rate of ATC and due to the importance of early intervention in minimizing catastrophic airway compromise.- Differential considerations/mimics can include primary thyroid lymphoma, SCC of the head and neck, and metastatic cancer (especially from lung).
- Early assessment of tumor mutations is key in expanding therapeutic options.
- Attain multidisciplinary team engagement and coordination
Coordinate early multidisciplinary involvement of surgeons, radiation and medical oncologists, endocrinologists, and palliative care teams to arrive at options for best care as outlined below. - Determine extent of disease
- Staging with imaging is required to classify as stage IVA, IVB, IVC; this is best done with FDG PET/CT and/or alternatively with dedicated body CT or MR imaging.
- Extent of local invasion must also be evaluated in parallel to assist in surgical decision making, and requires laryngoscopy.
- Undertake patient counseling in order to establish individualized patient goals of care
Counseling must be provided by a team/individuals skilled in the surgical, medical, and palliative management of complex thyroid malignancies in which tradeoffs counterbalancing risks and benefits with goals of care are completely discussed. This counseling should best involve not only the patient but also involve supportive individuals/family members. - Evaluate Surgical Options
- The primary goals in stages IVA and IVB ATC patients within an aggressive approach to their care are complete resection and prompt transition to adjuvant definitive-intention therapy, as long-term survival may be attainable. Thus, surgical procedures should not generate a wound or result in complications that would prevent chemotherapy and radiation onset due to the risk of wound breakdown given the lack of data supporting an association between increased extent of surgery and improved survival outcomes.
- In IVC ATC, the limited benefit resulting from surgery must be carefully tempered in consideration of other available palliative approaches, including radiation and systemic therapy.
- Surgical decision making
Rapidly assess resectability determining tumor invasion of the larynx, trachea, esophagus and status of the major vessels of the neck. Consider the need for tracheotomy, extent of thyroidectomy, neck dissection, and the need to avoid laryngectomy, esophageal resection, and major vessel reconstruction. Balancing morbidity from surgery with expected benefits within the context of patient anticipated prognosis and individualized goals of care is paramount.
Considerations:- Performance score/status
- Presence of distant metastasis
- Extent of local invasion of trachea and esophagus
- Need for urgent tracheostomy, understanding that placement of a tracheostomy results in immediate improvement in upper airway obstruction but requires significant education for care and understanding that tumor location and growth may make management of the tracheotomy complex
- Patient goals of care and willingness to accept anticipated morbidity of planned surgery
- Non-surgical management decision making
Other than surgery, options may include post-operative or primary chemoradiation versus palliative radiotherapy, systemic therapy or best supportive care considered within the context of:- Patient goals of care and willingness to accept anticipated toxicities of presented options
- Patient performance status and comorbidities and their impacts on feasibility of planned care
- Trade-offs from one approach to care versus alternatives
- Keep hospice/end of life care discussions in the foreground
- Given the historically dire prognosis of ATC, especially if stage IVC, hospice should always be presented among care options.
- Truth telling and realistic presentation of anticipated prognosis are critical in allowing sound patient decisions within their individual goals of care.
- For some patients, hospice may be preferable—even from the outset—in comparison with other alternative care options.
Terms and Definitions
TNM Staging
Extent of Resection
Adjuvant Therapy and Neoadjuvant Therapy
Oligometastatic Disease
Definition of Therapeutic Terms
Standard Radiation Prescription
Altered Fractionation
Radiotherapy Dose
Definitive-intention radiotherapy is high-dose radiation given with or without concurrent chemotherapy with the intent of maximizing the chance of long-term local control. Examples range from 50 Gy in 20 fractions, 2.5 Gy per fraction over 4 weeks at the low end, to 70 Gy in 35 fractions, 2 Gy per fraction over 7 weeks at the high end.
Palliative-intention Radiotherapy is lower dose radiotherapy given over a shorter time period with the primary aim of improving local symptoms and achieving initial disease control while minimizing hospital/clinic visits. This may be directed to the primary tumor or to metastases. Typical examples could be 20 Gy in 5 fractions, 4 Gy per fraction over 1 week and 30 Gy in 10 fractions, 3 Gy per fraction over 2 weeks.
Conformal Radiation
Intensity Modulated Radiotherapy (IMRT)
Radiosurgery and Stereotactic Body Radiotherapy (Stereotactic Radio-surgeries)
Concurrent Chemoradiation
Chemotherapy
Genomic Tumor Assessment
Genetically-informed Targeted Therapy
Bridging Therapy
RECIST Response
Diagnosis
...agnosis...
...logy, Histopathology, And Differential Diagnos...
...ommendation 1FNA cytology can play an i...
...ation 2Every effort should be made t...
...3Routine surgical pathology evaluation of r...
...4Once ATC diagnosis is considered, assessm...
...commendation 5Molecular profiling should be perfo...
...ial Evaluations
...tion 6Initial radiological tumor staging s...
...tice Statement 1In the event that...
...ice Statement 2All critical appointm...
...commendation 7Every patient with ATC should un...
Table 2. Panel of Routine Immunohistochemical Mark...
...Evaluation for Staging, Tests, and Proce...
Treatment
Treatment
...blishing Goals of Car...
...endation 8Comprehensive disease-specific mult...
...tatement 3Patients must have understandin...
...ce Statement 4Patients should be encouraged t...
...actice Statement 5A “goals-of-care” d...
...tion 9The treatment team should inc...
...ommendation 10The treatment team should...
...on 11At all stages of palliative care and hospi...
...cal Management of A...
...ion 12For patients with confined (stage...
...tion 13Radical resection (including laryng...
...ctice Statement 6If surgery is undertaken, int...
...e Statement 7In patients without impe...
...erapy and Systemic Chemotherapy in Loco...
Recommendation 14Following R0 or R1 r...
...od Practice Statement 8Radiation thera...
...Practice Statement 9Patient goals of...
...actice Statement 10Cytotoxic chemothera...
...ion 15The ATA recommends that patients who have...
...16In patients with unresectable disea...
...ice Statement 11In patients of poor performance s...
...mendation 17Among patients who are to re...
Recommendation 18The use of cytotoxic chemotherap...
...utic Approaches to Locally Advanced...
...dation 19Among ATC patients with unresect...
...ecommendation 20In BRAFV600E-mutated...
...21In BRAFV600E-mutated unresectable...
...dation 22In BRAF non-mutated patients, r...
...23In NTRK or RET fusion ATC patients with...
...dation 24In IVC ATC patients with high PD-L...
...ice Statement 12Patients with BRAF wild-typ...
...25In metastatic ATC patients lacking...
...Statement 13Therapeutic decision-making...
...Practice Statement 14Since prognosis is d...
...tion 26In ATC patients considering therapy,...
...mmendation 27In ATC patients with neur...
...ommendation 28In ATC patients with brain meta...
...e Statement 15Patients with brain m...
...roaches to Bone Metasta...
...ecommendation 29In patients with ATC with symptoma...
...ation 30In patients with ATC with b...
...mmendation 31In patients with ATC with bone...
...Practice Statement 16In patients on sy...
...oaches to Other Sites of Metas...
...erapy as described above is the first line of...
...roaches to Oligoprogressive Metastatic Disease...
...e Statement 16In patients on systemic therapy who...
...Initial Treatment of Stages IVA and IVB...
...2. Stage IVC...
...gure 3. ATC Suspected Clin...
...formed Consent ChecklistHaving trouble...
Table 5. Airway Evaluation, Inclusion, and Exclu...
...ples of Concurrent (in Combination with Radiation...