This is a phase II study for patients with thymoma or thymic carcinoma thought to be at significant risk for recurrence following surgical removal. This study involves the use of combined chemotherapy and radiation therapy prior to surgery, in hopes of increasing the chances of complete resection. The chemoradiotherapy protocol is one which has been used extensively for other diseases, and the side effects are therefore well-documented. Patients with thymomas thought to be at significant risk for recurrence (by x-ray and pathology criteria) will be allowed to participate, and will undergo combined chemotherapy with radiation to the chest followed by surgical removal of the tumor and postoperative chemotherapy. The main outcome measured will be the rate of pathological complete response (e.g. no active tumor in the resected specimen) to the preoperative treatment. Patients will receive postoperative treatment based on surgical and pathologic criteria.

Past experience has suggested that the ability to completely remove the thymoma using surgery is important in preventing recurrence. Strategies which would help the surgeon's ability to completely remove the tumor therefore need to be investigated.

This study represents a multi-institutional, phase II pilot trial of preoperative chemoradiotherapy followed by surgical resection and postoperative chemotherapy for patients with invasive thymoma or thymic carcinoma at significant risk for recurrence. We hypothesize that this strategy will be well-tolerated and produce response and resectability rates exceeding those previously published involving surgical resection alone, or preoperative chemotherapy followed by surgery. Patients with locally advanced thymoma, based on radiographic and biopsy criteria, will undergo pretreatment computed tomography (CT) scan and positron emission tomography (PET) followed by concurrent (simultaneous) chemotherapy (cisplatin and etoposide) and radiation. After this therapy, patients will be reassessed using computed tomography (CT) and PET, and undergo surgical resection of their tumors. Following resection, patients will be either observed, or treated with postoperative chemotherapy, or chemotherapy and radiation. Correlative genomic, serologic and pathologic studies will also be performed.

Inclusion Criteria:

• Biopsy-proven thymoma or thymic carcinoma.
• Invasive thymoma determined by specific radiographic criteria determined by CT scan.
• Acceptable kidney, liver, bone marrow, and respiratory functions.
• Karnofsy performance status greater than 80%.
• Patients must have a CT of the chest with IV contrast within 60 days of enrollment.
• Tumors larger than 8cm in greatest diameter on CT scan.
• For tumors 5-8cm in greatest diameter on CT scan, one or more of the following radiographic criteria must also be present on IV contrast CT Scan:
• Multifocal calcification
• Heterogeneous appearance
• Irregular of scalloped borders
• Obvious great vessel invasion or encirclement

Exclusion Criteria:

• Considered unable to medically tolerate surgical resection at the time of initial presentation.
• Radiographic evidence of stage IVA thymoma.
• Pretreatment biopsy showing WHO type A thymoma unless obvious great vessel invasion/encirclement is present on CT scan.
• Previous radiation therapy to the chest which would preclude the administration of radiation.
• Patents receiving other investigational drugs.