2023 Chinese Expert Consensus on Diagnosis and Treatment of Thymic Epithelial Tumors (English Core Interpretation)

1. Core Definitions & Epidemiology

• Thymic Epithelial Tumors (TETs)：Include thymoma (TM, A/AB/B1/B2/B3) and thymic carcinoma (TC, type C); all have malignant potential; incidence ~3.93/100,000 in China (higher than Western countries, race-dependent)PubMedPMC.
• Key Staging：
  • Masaoka-Koga (clinical treatment guidance): I (capsule-intact) → II (capsule invasion) → III (adjacent organ invasion) → IV (pleural/pericardial dissemination or distant metastasis)
  • AJCC/UICC 8th TNM (standard staging, recommended for registration/research)PMC.
   

2. Diagnosis (Strongly Recommended Consensus)

2.1 Imaging Workup

• 1st-line: Contrast-enhanced chest CT (mediastinal window) → assess size, invasion, lymph nodes, pleural/pericardial effusionPMCPMC.
• Supplementary:
  • MRI: Evaluate vascular/mediastinal invasion, distinguish cystic/solid lesionsPMC.
  • 18F-FDG PET/CT: Stage distant metastasis, differentiate TC (high SUV) vs. low-grade TM (low SUV); not for routine screeningPMC.
   
• Screening: Low-dose CT not recommended for general population (low incidence, no survival benefit); screen MG patients with chest CTPMC.

2.2 Pathological Diagnosis (Gold Standard)

• Core IHC: Pan-cytokeratin (AE1/AE3), CK5/6, P63, TTF-1 (exclude lung cancer), CD5/CD117 (TC marker), Ki-67 (proliferation)PMC.
• Biopsy: CT-guided core needle biopsy (standard); ultrasound-guided biopsy or thoracoscopic biopsy for specific cases; avoid fine-needle aspiration (FNA) alone (insufficient for subtyping)PMC.
• MiNEN (Mixed Neuroendocrine-Nonneuroendocrine Neoplasm): Report both components’ grade/proportion; treat per the more aggressive componentPMC.

2.3 Paraneoplastic Syndrome (Myasthenia Gravis, MG)

• Pre-op evaluation: Anti-AChR antibody, electromyography; optimize MG therapy (pyridostigmine, steroids) to reduce myasthenic crisis risk; thymectomy is first-line for TET-associated MGPMC.

3. Treatment Recommendations by Stage

3.1 Resectable TETs (Masaoka-Koga I–IIIA)

• Surgery (Strongly Recommended):
   
  • R0 resection (thymus + tumor + anterior mediastinal fat + regional lymph nodes [anterior mediastinal/cervical]) is the cornerstonePMC.
  • Approach: Median sternotomy (standard for invasion evaluation); thoracoscopic/laparoscopic minimally invasive surgery (MIS) for early-stage (I–II) (comparable OS/RFS to open, less morbidity)PMC.
  • Extended resection: Resect pericardium, pleura, lung, phrenic nerve, or vascular structures if involved (to achieve R0)PMC.
   
• Postoperative Adjuvant Therapy
   

  Stage/Pathology	Adjuvant Recommendation	Evidence
  I (R0, any TM)	No PORT/chemo	Strong, B
  IIA (R0, low-grade TM)	Optional PORT (no OS benefit)	Weak, B
  IIB–III (R0, B2/B3/TC)	PORT (50–54Gy, IMRT) + optional chemo	Strong, B
  R1/R2 resection	PORT (54–60Gy) + concurrent/sequential chemo	Strong, B
  TC (any stage II–III)	PORT (improves local control/OS)	Strong, B

   

3.2 Locally Advanced Unresectable TETs (IIIB–IV, No Distant Metastasis)

• First-line: Concurrent chemoradiotherapy (CCRT) (Strongly Recommended, A)
  • Regimen: Etoposide + Cisplatin (EP) + IMRT (50.4–54Gy, 1.8Gy/fr)
  • ORR ~85.7%, 5-year OS ~56.2% (Chinese phase II data)PMC.
   
• Induction therapy: Neoadjuvant chemo (EP/CAP [cyclophosphamide+doxorubicin+cisplatin]) ×2–3 cycles → resect if downstaged (Weak, C)PMC.
• Palliative RT: 30–36Gy for symptom relief (obstruction/pain) (Strong, B)PMC.

3.3 Metastatic/Recurrent TETs (IVB)

• First-line systemic therapy (Strongly Recommended, A):
  • Preferred: CAP (cyclophosphamide 500mg/m² d1 + doxorubicin 50mg/m² d1 + cisplatin 50mg/m² d1, q3w) → ORR ~50–70% (gold standard for TM/TC)
  • Alternative: EP (etoposide 100mg/m² d1–3 + cisplatin 25mg/m² d1–3, q3w) → better tolerance for elderly/comorbidities
  • TC: Consider carboplatin (AUC 5–6) instead of cisplatin for renal impairmentPMC.
   
• Second-line therapy (Weak, B/C):
  • Chemo: Paclitaxel (175mg/m² q3w), pemetrexed (500mg/m² q3w), gemcitabine + docetaxel
  • Targeted: Sunitinib (anti-angiogenic, ORR ~10–15%), everolimus (mTORi, for recurrent TM)
  • Immunotherapy: Anti-PD-1/PD-L1 (pembrolizumab/nivolumab) → ORR ~10–20% (higher in TC; caution: immune-related myositis/myasthenia in MG patients)PMC.
   
• Palliative care: Pleurodesis for malignant effusion; stent for airway/esophageal obstruction; nutrition support (Strong, B)PMC.

4. Follow-up (Strongly Recommended, B)

5. Key Consensus Highlights & Clinical Takeaways

1. R0 resection is paramount for all resectable TETs; MIS is feasible for early-stage.
2. PORT is indicated for IIB–III (B2/B3/TC) and R1/R2 resection; avoid for stage I R0.
3. CAP is first-line chemo for advanced/metastatic TETs; EP is a well-tolerated alternative.
4. Immunotherapy is promising but cautious in MG patients (risk of immune myasthenia).
5. MDT (thoracic surgery + medical oncology + radiation oncology + pathology + neurology) is mandatory for optimal management.