Guideline sources The following summarized guidelines for the evaluation and management of thymic epithelial tumors (TET) are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2015). 1 Calculator Calculator IASLC/ITMIG staging system for TNM classification for thymic tu Guidelines 1. Screening and diagnosis Diagnosis: https://web.pathway.md/diseases/recaFs8FaZMvaUjZT 1/5 6/24/23, 4:06 PM Thymic epithelial tumors Pathway Suspect thymoma as the first diagnosis in patients with a mediastinal mass associated with autoimmune disease. B Diagnose TET based on the differential diagnosis with other anterior mediastinal tumors and non-malignant thymic lesions. E 2. Classification and risk stratification Classification: classify TET according to the WHO histopathological classification. E Consider using the WHO classification for small biopsies, although it is designed for surgical resection specimens. B Staging: Use the Masaoka-Koga system (assessable only after surgical resection of the tumor) as the standard system for staging TET: Situation Guidance Macroscopically and microscopically completely encapsulated Stage I Microscopic transcapsular invasion Stage IIa Macroscopic invasion into surrounding fatty tissue, or macroscopically adherent to but not through mediastinal pleura or pericardium Stage IIb III Stage Pleural or pericardial dissemination Stage IVa Lymphogenous or hematogenous metastasis. B Stage IVb Consider using the proposed IASLC/ITMIG TNM system for staging TET. C 3. Diagnostic investigations Diagnostic imaging: obtain contrast-enhanced chest CT as standard imaging for thymic tumors. B Show 2 more Laboratory tests: obtain systematic immunological evaluations, including complete blood cells count with reticulocytes and SPEP, as well as ANA and anti-AChR antibodies. B https://web.pathway.md/diseases/recaFs8FaZMvaUjZT 2/5 6/24/23, 4:06 PM Thymic epithelial tumors Pathway 4. Diagnostic procedures Biopsy and histopathology: do not perform a pre-treatment biopsy if the diagnosis of a thymic epithelial tumor is highly suspected and upfront surgical resection is achievable. D Perform biopsy in all other clinical situations. D Show 5 more 5. Medical management General principles: Avoid performing therapeutic intervention in patients with a lesion < 30 mm given the low risk of progression or thymic malignancy. D Decide on the treatment strategy in patients with TET primarily based on whether the tumor may be resected upfront or not. B Adjuvant chemotherapy: do not offer postoperative chemotherapy after R0-R1 resection of a thymoma. D Show 2 more Induction chemotherapy: offer upfront, primary/induction chemotherapy as part of a curative- intent sequential strategy integrating subsequent surgery or radiotherapy if complete resection is deemed not to be achievable. E Offer primary/induction chemotherapy as the standard of treatment in patients with non-resectable locally advanced TET B Offer palliative chemotherapy only in patients ineligible for local treatment. E Show 4 more Definitive chemotherapy: offer chemotherapy as the single modality treatment in patients with advanced, non-resectable, non-irradiable or metastatic TET. B Show 3 more Targeted therapy: consider obtaining KIT sequencing (exons 9-17) in patients with refractory thymic carcinomas in the setting of potential access to specific inhibitors, particularly in the context of clinical trials. C Show 3 more Management of autoimmune syndromes: Integrate the management of autoimmune syndromes in the oncological management of patients with thymic tumors. B Educate patients with clinical myasthenia gravis or even isolated positive anti-AChR antibodies about the risks of myasthenic crisis in specific situations, such as stress or administration of certain drugs. B 6. Therapeutic procedures https://web.pathway.md/diseases/recaFs8FaZMvaUjZT 3/5 6/24/23, 4:06 PM Thymic epithelial tumors Pathway Adjuvant radiotherapy (indications): do not offer postoperative radiotherapy after complete resection of Masaoka-Koga stage I thymoma. D Show 6 more Adjuvant radiotherapy (technical considerations): initiate postoperative radiotherapy within 3 months of the surgical procedure. B Use 3D conformal radiotherapy or intensity-modulated radiotherapy targeted to the tumor bed. B Show 6 more Definitive radiotherapy: offer definitive radiotherapy as part of a sequential chemoradiotherapy strategy in patients ineligible for surgery. B Consider offering a combination with chemotherapy including cisplatin, etoposide chemotherapy, and a total dose of radiation of 60-66 Gy. B 7. Surgical interventions Upfront surgery (indications): Assess resectability mostly based on the surgeon's expertise. Discuss indications for surgery in a multidisciplinary tumor board setting. B Perform surgery as the first step of the treatment if complete resection is deemed to be achievable upfront. B Upfront surgery (technical considerations): use median sternotomy as the standard approach for surgery. B Perform complete thymectomy including the tumor, the residual thymus gland, and perithymic fat. B Show 10 more Debunking surgery: Consider performing subtotal (debulking) resection as an option in selected patients with thymoma aiming at facilitating subsequent definitive radiotherapy. C Do not perform debulking surgery in patients with thymic carcinoma. D 8. Follow-up and surveillance Follow-up imaging: obtain a chest CT 3-4 months after surgery. B Show 3 more Management of recurrence: manage recurrences of TET according to the same strategy as newly diagnosed tumors. B Show 5 more References 1. N Girard, E Ruffini, A Marx et al. Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v40 55. Open https://web.pathway.md/diseases/recaFs8FaZMvaUjZT 4/5 6/24/23, 4:06 PM Thymic epithelial tumors Pathway 2. Frank C Detterbeck, Kelly Stratton, Dorothy Giroux et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014 Sep;9 9 Suppl 2 S65 72. Open https://web.pathway.md/diseases/recaFs8FaZMvaUjZT 5/5