Adjuvant therapy for DTC

Approach:

• Risk stratify the patient
  • Imaging findings
  • Operative findings
  • Histopathology
  • Molecular testing if available
• Give levothyroxine to suppress TSH
• Give RAI if indicated
• Consider EBRT
• Dynamic risk stratification: reclassify and alter treatment accordingly as more information becomes available throughout follow-up

ATA risk stratification system to estimate risk of persistent/recurrent disease

Low risk Papillary thyroid cancer with all of the following present: No local or distant metastases All macroscopic tumor has been resected No invasion of locoregional tissues Tumor does not have aggressive histology (aggressive histologies include tall cell, insular, columnar cell carcinoma, Hürthle cell carcinoma, follicular thyroid cancer, hobnail variant) No vascular invasion No 131I uptake outside the thyroid bed on the post-treatment scan, if done Clinical N0 or ≤5 pathologic N1 micrometastases (<0.2 cm in largest dimension)* Intrathyroidal, encapsulated follicular variant of papillary thyroid cancer* Intrathyroidal, well-differentiated follicular thyroid cancer with capsular invasion and no or minimal (<4 foci) vascular invasion* Intrathyroidal, papillary microcarcinoma, unifocal or multifocal, including BRAF V600E mutated (if known)*

Intermediate risk Any of the following present: Microscopic invasion into the perithyroidal soft tissues Cervical lymph node metastases or 131I avid metastatic foci in the neck on the post-treatment scan done after thyroid remnant ablation Tumor with aggressive histology or vascular invasion (aggressive histologies include tall cell, insular, columnar cell carcinoma, Hürthle cell carcinoma, follicular thyroid cancer, hobnail variant) Clinical N1 or >5 pathologic N1 with all involved lymph nodes <3 cm in largest dimension* Multifocal papillary thyroid microcarcinoma with extrathyroidal extension and BRAF V600E mutated (if known)*

High risk Any of the following present: Macroscopic tumor invasion Incomplete tumor resection with gross residual disease Distant metastases Postoperative serum thyroglobulin suggestive of distant metastases Pathologic N1 with any metastatic lymph node ≥3 cm in largest dimension* Follicular thyroid cancer with extensive vascular invasion (>4 foci of vascular invasion)*

TSH suppression

• Rationale: prevent TSH stimulating ectopic thyroid tissue, with lifelong levothyroxine. Improves overall survival, but no clear best degree of suppression.
• Low-risk:
  • Detectable Tg: TSH 0.1 - 0.5 mU/L
  • Undetectable Tg: TSH 0.5 to 2 mU/L
• Intermediate: TSH 0.1 - 0.5 mU/L
• High: TSH < 0.1 mU/L
• Long-term, have to balance benefits of TSH suppression with clinical risks of hyperthyroidism, such as osteoporosis and AF
• If patients have excellent response to therapy, consider relaxing target

Radioiodine ablation

• Tumour type and operation
  • Useful with PTC and FTC
  • Commonly given with HCC too, although not as effective
  • Not given for PDTC, MTC and ATC
  • Obviously contraindicated if only hemithyroidectomy was performed
• Risk profile
  • Low-risk: not routinely given
  • Intermediate risk: selective but usually give at lower dose like 30mCi (microscopic or vascular invasion, significant lymph node metastases, aggressive histology)
  • High-risk: give, usually at a higher dose like 100mCi
• Indications
  • Ablate residual normal thyroid tissue (increase specificity of serum Tg for surveillance; prevent subsequent de novo cancer; treat microscopic disease)
  • Treat clinically detectable disease not addressed by surgery
• Protocol
  • Should be administered in a low-iodine state and high TSH levels, to maximise RAI uptake by thyroid tissue
  • Patient needs to be in isolation for 24-48 hours
  • Improves disease-free survival via ablation of residual or metastatic disease
  • Remnant ablation dose - 30-50mCi
  • Treatment dose - 100-150mCi
  • Pregnancy and breastfeeding are absolute contraindications; don't become pregnant for six months afterwards
  • Risks - sialadenitis, nasolacrimal duct obstruction, transient tumour/thyroid swelling, infertility, development of secondary malignancies (leukaemia)

Also consider adjuvant external beam radiation therapy

• Local control of unresectable locally advanced macroscopic or microscopic residual disease after thyroidectomy (especially RAI non-avid)
• Treatment of symptomatic distant metastatic foci that are RAI non-avid