ORIGINAL ARTICLE Adjuvant Radiotherapy for Thymic Epithelial Tumor Treatment Results and Prognostic Factors Yulia Kundel, MD,* Alon Yellin, MD,‡ Aron Popovtzer, MD,* Raphael Pfeffer, MD,† Zvi Symon, MD,† David A Simansky, MD,‡ Bernice Oberman, MD,§ Siegal Sadezki, MD,§ Baruch Brenner, MD,* Raphael Catane, MD,† and Mark L. Levitt, MD† Objective: To determine whether the use of adjuvant radiation in the treatment of invasive thymic tumors affects survival and to identify prognostic factors. Methods: The files of 47 patients with thymic tumors treated by adjuvant radiation in our institute from 1984 to 2003 were reviewed for data on prognosis and survival. All patients underwent thoracot- omy followed by either total macroscopic resection (n = 42) or biopsy (n = 5). The radiation dose ranged from 26 to 60 Gy. Results: Median duration of follow-up was 10.6 years. Overall 5-year survival was 73% (60%– 88%): 77% for thymoma (n = 35/45) versus 33% for thymic carcinoma (n = 2/6) ( P = 0.14). Better survival was associated with lower disease stage (II vs. III/IVA, P = 0.01), resection (P = 0.0004), myasthenia gravis at presentation (P = 0.04), and higher radiation dose (45 vs. 45 Gy, P = 0.02); sex, smoking, tumor size, pathology, and margin status had no effect. Locoregional relapse occurred in 11 patients and distant metastasis in 4. The 5-year disease-free survival was 67% (52%– 86%), with a median time to recurrence of 8.3 years. The better overall survival and disease-free survival associated with higher doses of radiation were also true for stage II patients. On multivariate analyses after adjusting for age, higher disease stage and lower radiation dose were found to adversely affect overall survival and disease-free survival. Thymic carcinoma had an impact only on disease-free survival. Conclusion: Postoperative radiation therapy to doses above 45 Gy may improve the disease-free and overall survival of patients with invasive thymoma, especially stage II. Thymic carcinoma has a worse prognosis. Key Words: thymic epithelial tumor, invasvie thymoma, thymic carcinoma, adjuvant radiotherapy. (Am J Clin Oncol 2007;30: 389 –394) T hymic epithelial tumors are characterized by a low inci- dence, wide ranging histologic appearance, and unique biologic behavior. Macroscopic and microscopic signs of invasiveness at the time of surgery are recognized prognostic factors, and the extent of tumor invasion forms the basis for the most widely used clinical staging system, described by Masaoka et al. 1 The prognostic impact of tumor histopathol- ogy is still unclear. 2 An aggressive surgical approach has long been considered the mainstay of therapy. Complete resection is associated with better survival than subtotal resection with neoadjuvant or adjuvant chemotherapy or radiotherapy. 3–7 Many authors advocate the use of adjuvant radiation also with complete resection; but because of the relative rarity of these tumors, its efficacy has not been evaluated in randomized studies. The aim of the present study was to review our expe- rience with adjuvant radiation in the treatment of invasive and thymic epithelial tumors and to identify prognostic factors for recurrence and survival. MATERIALS AND METHODS Patient Characteristics The records of patients with thymic tumors treated by adjuvant radiation between 1984 and 2003 at Sheba Medical Center were reviewed. There were 29 men and 18 women 20 to 78 years of age (median, 50 years). Their clinical charac- teristics are shown in Table 1. Staging The clinical workup included a detailed medical his- tory, physical examination, chest x-ray, blood tests, and chest computed tomography. Staging was based on the surgical and pathologic criteria described by Masaoka et al 1 in 1981 and modified in 1994 8 (Table 2). Thirty-three patients had Masaoka stage II disease, 12 had stage III, and 2 had stage IVA. Average tumor size was 6.4 cm in diameter (range, 2–12 cm). Pathology The diagnosis of thymoma was based on the pathologic classification of Rosai and Levine, 9 ie, neoplasms of thymic epithelial cells, regardless of the presence of a lymphoid component. Thymic tumors containing cells with cytologic From the *Department of Oncology, Rabin Medical Center, Beilinson Campus, Petach Tikva; †Institute of Oncology, ‡Department of Thoracic Surgery, and §Gertner Institute of Epidemiology and Health Policy Research, Cancer Epidemiology Unit, Chaim Sheba Medical Center, Tel Hashomer; both centers affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Reprints: Yulia Kundel, MD, Department of Oncology, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel. E-mail: yuliak@ clalit.org.il. Copyright © 2007 by Lippincott Williams & Wilkins ISSN: 0277-3732/07/3004-0389 DOI: 10.1097/COC.0b013e318042d566 American Journal of Clinical Oncology • Volume 30, Number 4, August 2007 389