Advancements in the Treatment of Differentiated Thyroid Cancer (DTC)

Radioiodine Ablation

• The American Thyroid Association (ATA) recommends radioiodine (RAI) adjuvant therapy for:
  • High risk DTC patients after total thyroidectomy
• Prior to RAI therapy:
  • Serum TSH, thyroglobulin (Tg), and anti-Tg antibody measurements should be obtained
• Patients should be instructed to:
  • Maintain a low iodine diet (50 mg / day) for 1 to 2 weeks
  • And undergo thyroid hormone withdrawal
• Levothyroxine (LT4):
  • Should be discontinued 3 to 4 weeks prior to RAI, and
• Liothyronine (LT3):
  • Should be discontinued 2 weeks prior to therapy
• ATA low and intermediate risk DTC patients and patients with contraindications to a hypothyroid state:
  • May undergo recombinant human TSH stimulation instead of thyroid hormone withdrawal
• The 5-year follow-up results of the ESTIMABL1 trial:
  • A randomized control trial investigating rhTSH versus thyroid hormone withdrawal and low activity (1.1 GBq) versus high activity (3.7GBq) RAI in patients with low-risk DTC:
    • Showed no evidence of disease regardless of preparation method or radioiodine dose used, providing further support for the use of rhTSH and 1.1 GBq radioactive iodine in these patients
• For advanced DTC:
  • Dosimetry might be appropriate to quantify RAI uptake and determine dosing given the variability from person to person, and within cells of the same tissue
• The goals of RAI therapy include:
  • Destroying occult disease foci
  • Eliminating residual healthy tissue that may serve as a locus for neoplastic transformation
  • Improving the specificity of Tg as a tumor marker, and of whole body RAI scans during long-term surveillance
• A dose of 30mCi is recommended over higher doses in lower-risk patients, but high-risk patients may require 100 to 200 mCi
• During RAI ablation, 131I is taken up by follicular thyroid cells, where the molecules accumulate and undergo beta decay:
  • This process is optimized by functional sodium iodide symporter expression (NIS):
    • Dedifferentiating tumors lose NIS expression and become fluorodeoxyglucose (FDG) avid as they lose RAI avidity:
    • For this reason, FDG-PET (positron emission tomography) positive tumors:
      • Tend to be more aggressive and unlikely to respond to RAI
• Age greater than 40 years, large tumor burden, and Hürthle cell histology:
  • Are also indicators of poor response
• MAPK and PI3K / AKT activation:
  • Is thought to decrease NIS activity
• Tumors with RAS mutations may be more likely to be RAI avid than those with BRAF and TERTmutations
• Side effects of RAI therapy include:
  • Nausea
  • Temporary or permanent salivary gland and lacrimal duct dysfunction
  • Sialadenitis
  • Parotitis
  • Thyroiditis
  • Bone marrow and gonadal dysfunction
    • Adequate hydration might help alleviate symptoms
  • There is also a risk of second primary cancer of:
    • Soft tissue, salivary gland, colon, and blood, associated with higher cumulative doses
• Less than 10% of DTC patients will develop metastatic disease
  • Of these, approximately one in three experience complete remission after RAI therapy
• The ATA recommends a whole body scan with or without single photon emission computed tomography (SPECT) / computed tomography (CT) to determine RAI avidity for residual structural disease after therapy

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