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
Diagnos...
...gy, Histopathology, And Differential Dia...
...mendation 1FNA cytology can play an important di...
...ion 2Every effort should be made to...
...tion 3Routine surgical pathology evalua...
...Once ATC diagnosis is considered, assessment...
...ndation 5Molecular profiling should be performed a...
...itial Evaluation...
...mendation 6Initial radiological tumor sta...
...tatement 1In the event that biopsy of a...
Good Practice Statement 2All critical...
...ecommendation 7Every patient with ATC should...
...el of Routine Immunohistochemical Mar...
.... Initial Evaluation for Staging, Tests,...
Treatment
...reatment
...stablishing Goals of C...
...mmendation 8Comprehensive disease-specific m...
...Statement 3Patients must have underst...
...tice Statement 4Patients should be encouraged to d...
...Statement 5A “goals-of-care” discussion shoul...
...commendation 9The treatment team should include...
...ommendation 10The treatment team should engage...
...endation 11At all stages of palliat...
...rgical Management of AT...
...endation 12For patients with confined (stag...
Recommendation 13Radical resection (includi...
Good Practice Statement 6If surgery is undertake...
...Statement 7In patients without impending airway...
...nd Systemic Chemotherapy in Locore...
...endation 14Following R0 or R1 resection, the AT...
...Statement 8Radiation therapy should b...
...od Practice Statement 9Patient goals of care,...
...ce Statement 10Cytotoxic chemotherapy can be initi...
...ecommendation 15The ATA recommends tha...
...mendation 16In patients with unres...
...e Statement 11In patients of poor perf...
...ndation 17Among patients who are to rec...
...dation 18The use of cytotoxic chemothera...
...apeutic Approaches to Locally Advanced Unr...
...ndation 19Among ATC patients with unresectable...
...mmendation 20In BRAFV600E-mutated IVC...
...endation 21In BRAFV600E-mutated unresectable stage...
...2In BRAF non-mutated patients, radiatio...
...23In NTRK or RET fusion ATC patients with s...
...endation 24In IVC ATC patients with high PD-L1...
...tatement 12Patients with BRAF wild-type...
...ion 25In metastatic ATC patients lacki...
...ice Statement 13Therapeutic decision-making in th...
...ood Practice Statement 14Since prognosis is di...
...dation 26In ATC patients considering therapy...
...7In ATC patients with neurologic brain...
...on 28In ATC patients with brain metastases referra...
Good Practice Statement 15Patients w...
...hes to Bone Metastase...
...on 29In patients with ATC with symptomatic o...
...ion 30In patients with ATC with bone...
...ommendation 31In patients with ATC with bone meta...
...Statement 16In patients on systemic ther...
...ches to Other Sites of Metas...
...py as described above is the first...
...roaches to Oligoprogressive Metastat...
...Statement 16In patients on systemic...
...Initial Treatment of Stages IVA and IVB...
...gure 2. Stage IVC...
...3. ATC Suspected Clinically+...
...4. Informed Consent ChecklistHaving trouble...
...ble 5. Airway Evaluation, Inclusion, and E...
Table 6. Examples of Concurrent (in Combinat...