What is the role of radiotherapy in the treatment of Medullary Thyroid Cancer (MTC)?

Role of Radiotherapy in Medullary Thyroid Cancer

Radiotherapy is often used in the presence of local invasion in MTC, particularly for patients with extrathyroidal extension, positive margins, or high-volume nodal disease with extranodal extension, though it provides locoregional control without improving overall survival. 1

Adjuvant Radiotherapy Indications

Postoperative adjuvant radiotherapy should be considered for high-risk patients with:

• Gross extrathyroidal extension (T4a or T4b) with positive margins after resection of all gross disease 1
• Moderate- to high-volume disease in central or lateral neck lymph nodes with extranodal soft tissue extension 1
• Microscopic residual disease, extraglandular invasion, or lymph node involvement - these patients achieve 86% locoregional relapse-free rate at 10 years with radiotherapy versus 52% without (p=0.049) 2

A systematic review of approximately 1200 patients demonstrated that radiotherapy reduces locoregional relapse risk by at least 38%, particularly in patients with nodal involvement, extrathyroidal extension, or residual disease. 3

Technical Considerations

When external-beam radiotherapy is administered:

• Dose: 40 Gy in 20 fractions to cervical, supraclavicular, and upper mediastinal lymph nodes over 4 weeks, with booster doses of 10 Gy in 5 fractions to the thyroid bed 1
• Higher doses of 60 Gy or greater are recommended based on evidence of improved outcomes 3
• Timing: Interval between surgery and radiotherapy should be less than 2 months for optimal efficacy 3

Palliative Radiotherapy

External-beam radiotherapy can be given to:

• Palliate painful or progressing bone metastases 1
• Treat unresectable locoregional disease - 21% (13/63 patients) achieved complete response with radiotherapy for unresectable disease 3
• Provide sustained symptom relief at metastatic sites - durable control achieved in 45% of palliatively treated metastatic sites 4

Important Limitations and Caveats

Radiotherapy does NOT improve overall survival in MTC - four cohort studies consistently showed no significant effect on overall survival, though locoregional control is improved. 3 This is a critical distinction from its role in other thyroid cancers.

This practice is rarely recommended in children despite potential benefits in adults. 1

Acute toxicity includes difficulty swallowing, xerostomia, and skin reactions, while late morbidity is infrequent with low incidence of persistent xerostomia. 3

Clinical Algorithm for Decision-Making

Consider adjuvant radiotherapy if ANY of the following are present:

1. Gross extrathyroidal extension with positive margins 1
2. High-volume nodal disease with extranodal extension 1
3. Microscopic residual disease with extraglandular invasion 2
4. Multiple involved lymph nodes 3

Omit radiotherapy if:

• Complete resection achieved with negative margins and no extranodal extension 1
• Pediatric patient (unless exceptional circumstances) 1

Use palliative radiotherapy for:

• Symptomatic bone metastases 1
• Unresectable locoregional disease causing symptoms 3, 4