What is the treatment approach for a patient diagnosed with thymoma?

Treatment of Thymoma

Complete surgical resection via open median sternotomy is the cornerstone of thymoma treatment, with stage-specific multimodality therapy determining the need for additional radiation or chemotherapy. 1

Stage-Based Treatment Algorithm

Stage I Disease

• Perform complete surgical resection of the entire thymus via open median sternotomy without any neoadjuvant or adjuvant therapy. 1
• Minimally invasive approaches (video-assisted thoracic surgery) are not recommended as they compromise oncologic outcomes. 1
• No postoperative radiation or chemotherapy is indicated for completely resected Stage I disease. 1
• For medically inoperable patients only, consider chemoradiation or radiation alone as definitive treatment. 1

Stage II Disease

• Complete surgical resection via open median sternotomy remains the standard approach. 1
• Adjuvant radiation therapy should be considered for high-risk features including: 1
  • Capsular invasion (Stage IIB)
  • Close or positive surgical margins
  • WHO histologic type B tumors
  • Tumor adherent to pericardium
• Routine adjuvant radiation is not recommended for Stage IIA disease with complete resection and favorable histology. 1
• Discuss radiation risks with younger patients, particularly secondary malignancies and coronary artery disease, as these patients may survive decades. 1
• Neither neoadjuvant nor adjuvant chemotherapy is recommended for Stage II disease. 1

Stage III Disease (Locally Advanced)

Initial Assessment

• Obtain tissue diagnosis via CT-guided core-needle biopsy or open surgical biopsy before initiating neoadjuvant therapy. 1
• Carefully evaluate for multimodality therapy including neoadjuvant chemotherapy, surgical resection, and adjuvant chemoradiotherapy. 1

Stage IIIA (Potentially Resectable)

• Surgery should be performed either initially or after neoadjuvant therapy, aiming for complete resection with wide surgical margins. 1
• If preoperative assessment suggests incomplete resection is likely, administer neoadjuvant chemoradiotherapy before surgery. 1
• Use cisplatin-based combination chemotherapy regimens (most experience with cisplatin plus anthracycline combinations). 1
• For small treatment volumes, concurrent chemoradiotherapy is preferred; for bulky tumors, use sequential chemotherapy followed by radiation. 1

Stage IIIB (More Extensive Local Disease)

• Assess for surgery only after neoadjuvant chemoradiotherapy. 1
• If complete resection is not achievable at thoracotomy, perform maximal debulking with vascular reconstruction as needed. 1
• Place surgical clips to mark residual tumor for targeted adjuvant radiation. 1
• Do not perform bilateral phrenic nerve resection due to severe respiratory morbidity. 1

Adjuvant Therapy for Resected Stage III

• Adjuvant radiotherapy is recommended for all Stage III disease. 1
• Adjuvant chemotherapy may be considered but insufficient data exists to routinely recommend it after complete resection. 1

Unresectable Stage III Disease

• Administer chemotherapy concurrent with or sequential to radiation therapy. 1
• Unresectable disease is defined as extensive tumor involving trachea, great arteries, and/or heart that has not responded to cisplatin-based chemotherapy. 1

Stage IVA Disease (Pleural/Pericardial Metastases)

• Apply Stage III treatment principles with the critical modification that surgery is only recommended if all pleural and pericardial metastases can be completely resected. 1
• Surgery should be considered either initially or after neoadjuvant therapy with complete resection as the goal. 1
• Neoadjuvant chemoradiotherapy is an option using cisplatin-based regimens. 1
• Adjuvant chemoradiotherapy is an option after resection. 1
• For unresectable Stage IVA with extensive pleural/pericardial metastases, chemotherapy is commonly provided, with concurrent or sequential radiation as an option. 1

Stage IVB Disease (Distant Metastases)

• Treatment must be individualized on a case-by-case basis; no generic recommendations exist due to heterogeneity of presentations. 1

Recurrent Disease

• Consider surgery, radiation, and/or chemoradiation based on location and extent of recurrence. 1
• Chemoradiation should be considered for all medically or technically inoperable recurrent disease. 1

Critical Management Considerations

Paraneoplastic Syndromes

• Screen all patients for myasthenia gravis (present in 30-50% of thymoma patients) before any intervention, as it must be medically controlled prior to surgery. 1, 2, 3
• Perform systematic immunological workup including anti-acetylcholine receptor antibodies, complete blood count with reticulocytes, serum protein electrophoresis, and anti-nuclear antibodies. 1, 2
• Evaluate for pure red cell aplasia (5% of cases) and hypogammaglobulinemia (5% of cases). 1

Surgical Principles

• Open median sternotomy is the required surgical approach; minimally invasive techniques are not standard of care. 1
• Complete resection with wide surgical margins is the primary determinant of survival. 1
• Resection should include the entire thymus from phrenic nerve to phrenic nerve laterally and from diaphragm to thyroid gland superiorly. 4

Radiation Therapy Considerations

• Limit total cardiac dose to ≤30 Gy in younger patients given long survival expectations and risk of coronary artery disease. 4
• Typical doses range from 45-70 Gy to the primary tumor bed for incomplete resection or advanced disease. 4

Surveillance

• Perform chest CT with contrast every 6 months for 2 years, then annually until 10 years, as thymomas have a tendency for late recurrence. 4

Common Pitfalls to Avoid

• Do not biopsy apparently resectable thymomas—proceed directly to surgical resection to avoid tumor seeding and treatment delays. 2
• Do not use minimally invasive surgical approaches as they compromise complete resection. 1
• Do not perform bilateral phrenic nerve resection even for extensive disease due to severe respiratory morbidity. 1
• Do not proceed to surgery without first medically optimizing myasthenia gravis to prevent perioperative myasthenic crisis. 2
• Do not forget to discuss radiation risks (secondary malignancies, coronary disease) with younger patients who may survive decades. 1