Therapeutic management of patients with advanced thymic malignancies: A review for clinicians.

Thymic epithelial tumors (TETs) are a heterogeneous group of rare tumors that arise from thymic epithelial cells in the anterior mediastinum. They can be divided into three different histological subtypes: thymomas, thymic carcinomas (TC), and neuroendocrine carcinomas (TNET). TCs and TNETs are rarer but more aggressive entities with frequent distant metastasis. Thymomas occur in 90 % of cases in a localized/locally advanced stage, on the other hand about 70 % of TCs are locally advanced at the time of diagnosis. Surgery plays a primary role in the management of patients in whom complete resection is feasible. The benefit of post-operative radiotherapy (PORT) is still controversial, since it could be related to stage, histotype, and preoperative chemotherapy. If the tumor is unresectable at diagnosis, radiotherapy or concurrent chemoradiotherapy is the most commonly used approach. Cisplatin and anthracycline-based regimens are standard of care in patients with unresectable or metastatic thymomas, but, at the same time, regimens with carboplatin and paclitaxel are the most widely used especially in patients with contraindications to cisplatin/anthracyclines, due to better tolerance. Recently, the anti-VEGFR antibody Ramucirumab has shown promising activity in combination with carboplatin plus paclitaxel in previously untreated advanced TCs. Several clinical trials with chemotherapy combination, target therapy and immunotherapy are still ongoing to define the best therapeutic strategy in this disease, also for the second line treatment, for which in daily practice there is currently no standard of care for patients who went into progression to the first line.