What is the role of external beam radiation therapy (EBRT) in the treatment of high-risk thyroid cancer patients with aggressive features, such as extrathyroidal extension, lymph node metastases, or distant metastases, and a history of thyroidectomy?

External Beam Radiation Therapy for High-Risk Thyroid Cancer

External beam radiation therapy (EBRT) should be considered for high-risk differentiated thyroid cancer patients with gross extrathyroidal extension (T4 disease), positive surgical margins after resection of all gross disease, or moderate-to-high volume lymph node disease with extranodal soft tissue extension. 1

Primary Indications for EBRT

EBRT is indicated in the following specific high-risk scenarios:

• Gross extrathyroidal extension (T4a or T4b disease) with positive margins after resection of all gross disease 2, 1
• Moderate-to-high volume central or lateral neck lymph node disease with extranodal soft tissue extension 2, 1
• Incomplete surgical excision when complete resection is not possible 2
• Absence of significant radioiodine uptake in tumors that would otherwise require adjuvant therapy 2

The American Joint Committee on Cancer specifically recommends EBRT for these indications, as radioactive iodine remains the primary adjuvant therapy but is ineffective when uptake is inadequate 1.

Technical Delivery Parameters

The standard EBRT regimen consists of:

• 40 Gy in 20 fractions to cervical, supraclavicular, and upper mediastinal lymph nodes over 4 weeks 2, 1
• Booster doses of 10 Gy in 5 fractions to the thyroid bed for a total of 50 Gy when indicated 2, 1
• Image-guided radiotherapy techniques should be utilized to maximize effectiveness and minimize toxicity 1

Intensity-modulated radiation therapy (IMRT) offers clear dosimetric advantages with reduced late toxicities to less than 5%, compared to older techniques 3.

Evidence for Locoregional Control

Retrospective data demonstrate improved locoregional control with EBRT in high-risk patients:

• In patients with microscopic residual disease, extraglandular invasion, or lymph node involvement, the 10-year locoregional relapse-free rate was 86% with postoperative EBRT versus 52% without EBRT (p=0.049) 4
• Five-year locoregional control rates of 88-89% have been reported in patients with locally advanced disease receiving high-dose EBRT 5
• Locoregional control is improved with doses exceeding 64 Gy, microscopic rather than macroscopic residual disease, and previously untreated tumors 5

Relationship to Radioactive Iodine Therapy

EBRT serves as a complementary modality when radioactive iodine is inadequate:

• Radioactive iodine remains the primary adjuvant therapy for differentiated thyroid cancer after total thyroidectomy 1
• EBRT is indicated when complete surgical excision is impossible or there is no significant radioiodine uptake in the tumor 2, 6
• For locoregional recurrent disease, treatment is based on combination of surgery and radioiodine therapy, with EBRT reserved for specific indications 2, 6

Medullary Thyroid Cancer Considerations

EBRT has a more established role in medullary thyroid cancer (MTC):

• Postoperative adjuvant EBRT should be considered for patients with gross extrathyroidal extension (T4a or T4b) with positive margins after resection of all gross disease 2
• EBRT is indicated for moderate-to-high volume disease in central or lateral neck lymph nodes with extranodal soft tissue extension 2
• Slight improvements in local disease-free survival have been reported for patients with extrathyroidal invasion or extensive locoregional node involvement 2

Palliative Applications

EBRT provides effective palliation for metastatic disease:

• Single fraction or fractionated courses achieve complete symptomatic responses in 20-25% of patients with bone metastases 1
• Stereotactic radiosurgery is preferred for solitary brain metastases 1
• Whole brain radiotherapy (20-30 Gy in 4-10 fractions) is used for multiple brain lesions 1
• EBRT can palliate painful or progressing bone metastases in both differentiated and medullary thyroid cancer 2

Critical Pitfalls to Avoid

Do not use EBRT in the following scenarios:

• Low-risk disease with unifocal tumors <1 cm, no extrathyroidal extension, and no lymph node metastases—these patients do not benefit from EBRT 1
• Routine adjuvant treatment after complete surgical resection of standard papillary thyroid carcinoma 1
• As a substitute for adequate surgery—the primary treatment remains total or near-total thyroidectomy with appropriate lymph node dissection when indicated 1
• In children except in exceptional circumstances, due to long-term toxicity concerns including secondary malignancies 2, 1

Effect on Survival

The impact of EBRT on overall survival remains uncertain:

• Retrospective studies show improved locoregional control but the effect on overall survival is unclear 7
• No randomized controlled trials are available to definitively establish survival benefit 7
• Five-year cause-specific survival of 80-86% has been reported in patients receiving EBRT for locally advanced disease 4, 5