Does radiotherapy still have a role in a patient with advanced Medullary Thyroid Cancer (MTC) and multiple lung metastases?

Radiotherapy in Advanced MTC with Lung Metastases

Yes, radiotherapy has a limited but specific palliative role in advanced medullary thyroid cancer with lung metastases, primarily for symptomatic bone lesions or local complications, but it does not improve overall survival and is not indicated for asymptomatic lung metastases themselves. 1, 2

Primary Treatment Approach for Metastatic MTC

The cornerstone of management for progressive metastatic MTC is systemic therapy with tyrosine kinase inhibitors, not radiotherapy. 1

• Cabozantinib and vandetanib are first-line systemic therapies for patients with progressive, metastatic MTC 1
• Systemic therapy should be initiated based on disease progression (RECIST v1.1 criteria), symptoms, high tumor burden, or lesions near vital structures 1
• Neither approved systemic therapy has demonstrated overall survival benefit, so timing of initiation requires careful consideration 1

Specific Indications for Radiotherapy in Metastatic MTC

Palliative External Beam Radiotherapy

External beam radiotherapy should be reserved for symptomatic metastases, particularly bone lesions causing pain or risk of fracture. 2, 3

• The National Comprehensive Cancer Network recommends external beam radiotherapy to palliate painful or progressing bone metastases 2
• Radiotherapy is often used for local invasion or symptomatic sites but does not provide survival benefit 1
• One case report demonstrated successful use of palliative radiotherapy for symptomatic bone lesions while lung metastases were managed with systemic therapy 3

Locoregional Radiotherapy

Radiotherapy may be considered for locoregional disease control in specific scenarios:

• Gross extrathyroidal extension with positive surgical margins 2
• High-volume nodal disease with extranodal extension 2
• Standard dosing is 40 Gy in 20 fractions to cervical/supraclavicular/upper mediastinal nodes, with 10 Gy boost to thyroid bed 2

What Radiotherapy Does NOT Address

Radiotherapy has no role in treating asymptomatic lung metastases in MTC. 1

• Lung metastases in MTC do not respond to radioactive iodine (unlike differentiated thyroid cancer) 1
• Chemotherapy and radiotherapy have shown minimal benefit (<20% response rate) for systemic disease control 1
• Metastasectomy or radiofrequency ablation may be considered for oligometastatic lung disease, but not radiotherapy 1

Clinical Decision Algorithm

For a patient with advanced MTC and multiple lung metastases:

1. Assess disease progression: Calculate calcitonin and CEA doubling times to predict disease behavior 1

2. If progressive disease or symptomatic:

   • Initiate systemic therapy with cabozantinib or vandetanib 1
   • Consider clinical trial enrollment 1

3. If bone metastases develop:

   • Use external beam radiotherapy for painful or high-risk skeletal lesions 2, 3
   • Consider bone resorption inhibitors (bisphosphonates/denosumab) 1

4. If locoregional disease with invasion:

   • Consider radiotherapy for local control if surgery incomplete 2

5. For lung metastases specifically:

   • Do NOT use radiotherapy 1
   • Consider RFA only for solitary symptomatic lesions 1
   • Rely on systemic therapy for disease control 1

Critical Pitfalls to Avoid

Do not delay systemic therapy while pursuing radiotherapy for metastatic disease. 1, 3

• Radiotherapy provides only local palliation, not systemic disease control 1, 4
• The presence of multiple lung metastases indicates systemic disease requiring systemic treatment 1
• Waiting for radiographic progression alone may be insufficient; consider progression rate, tumor burden, and symptom development 3

Do not confuse MTC management with differentiated thyroid cancer protocols. 1

• MTC does not concentrate radioactive iodine, so RAI therapy is ineffective 1
• External beam radiotherapy plays a much smaller role in MTC than in other thyroid cancers 1