Esra KORKMAZ KIRAKLI, Sevilay ERDEM, Mediha Tülin BOZKURT, Hasan YILMAZ

Role of radiotherapy in Masaoka stage II and III thymomas – single center experience

Aim: Thymomas are rare neoplasms. Complete surgical resection is the cornerstone of the treatment. The role of adjuvant radiotherapy (RT) in Masaoka stage II disease is controversial, but in more advanced stages and the role of radical RT in inoperable cases are clear. This study is conducted to evaluate local control, relapse free survival and overall survival rates in Masaoka stage II and III thymoma patients after adjuvant or radical RT. Materials and Methods: The medical records of thymoma patients who were treated and completed their RT course between January 2010 and August 2016 in a single center were evaluated retrospectively. Results: Twenty-two patients were available for analysis. Treatment planning was adjuvant in 18 patients and radical in 5 patients. Median age at diagnosis was 59 (50-62). Type of resection was R0 in all cases. The adjuvant RT dose was 50 Gy; radical RT dose was 60-66 Gy. The most common acute toxicity was grade 1 pneumonitis which was reported in 9 patients (39%). Grade 2 acute pneumonitis was experienced by 3 patients (13%), grade 2 acute esophagitis was experienced by 2 patients (9%). One patient had late grade 3 esophageal toxicity. Follow-up time ranged from 6 to 99 months, median 18 months, local control rate was 100%, relapse free survival (RFS) was 96%, cancer specific survival was 96%, 2 years overall survival (OS) was 83%. Conclusion: Although our results seem to be in concordance with the literature, longer follow-up is needed to be able to make a conclusion in terms of LC, RFS and OS, since thymoma has an indolent course with low relapse rate and long RFS.

Masaoka evre II ve III timomada radyoterapinin rolü - tek merkez deneyimi

Amaç: Timomalar oldukça nadir tümörlerdir. Tam rezeksiyon tedavinin ana öğesidir. Adjuvan radyoterapinin (RT) rolü Masaoka evre II hastalıkta tartışmalıyken, daha ileri evrelerde ve inoperabl olgularda nettir. Bu çalışma, evre II-III timoma olgularında adjuvan veya radikal RT sonrası lokal kontrol, yinelemesiz sağ kalım ve genel sağ kalım (GS) sonuçlarını araştırmak için planlandı. Gereç ve Yöntem: Ocak 2010-Ağustos 2016 arasında timoma tanısıyla RT uygulanan olguların medikal verileri geriye dönük olarak incelendi. Bulgular: Adjuvan RT uygulanan 18 ve radikal RT uygulanan 5, toplam 23 evre II-III olgu analizlere dahil edildi. Ortanca yaş 59 (50-62) idi. Opere olguların tümünde rezeksiyon R0 şeklindeydi. Adjuvan RT dozu 50 Gy, radikal RT dozu 60-66 Gy idi. En sık izlenen toksisite 9 olguda (%39) gelişen derece 1 pnömoni idi. Derece 2 pnömoni 3 olguda (%13), derece 2 özofajit 2 olguda (%9) izlenirken, 1 olguda geç dönem özofajial toksisite izlendi. İzlem süresi ortanca 18 aydı (6-99 ay). Lokal kontrol oranı %100, yinelemesiz sağ kalım oranı %96, kansere özgü sağ kalım %96, 2 yıllık GS oranı %83’tü. Sonuç: Sonuçlarımız literatür ile uyumlu görünmesine rağmen, timomanın yineleme oranı düşük ve yinelemesiz sağ kalımı uzun bir hastalık olması nedeniyle lokal kontrol, yinelemesiz sağ kalım ve GS sonuçlarımızla ilgili yorum yapabilmemiz için daha uzun izlem süresine ihtiyaç duyulmaktadır.

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1. Forquer JA, Rong N, Fakiris AJ, Loehrer PJ, Johnstone PA. Postoperative radiotherapy after surgical resection of thymoma: Differing roles in localized and regional disease. Int J Radiat Oncol Biol Phys 2010; 76 (2): 440-5.

2. Zhu G, He S, Fu X, Jiang G, Liu T. Radiotherapy and prognostic factors for thymoma: A retrospective study of 175 patients. Int J Radiat Oncol Biol Phys 2004; 60 (4): 1113-9.

3. Rena O, Papalia E, Maggi G, et al. World Health Organization histologic classification: An independent prognostic factor in resected thymomas. Lung Cancer 2005; 50 (1): 59-66.

4. Blumberg D, Port JL, Weksler B, et al. Thymoma: A multivariate analysis of factors predicting survival. Ann Thorac Surg 1995; 60 (4): 908-13.

5. Zhang H, Lu N, Wang M, Gu X, Zhang D. Postoperative radiotherapy for stage I thymoma: A prospective randomized trial in 29 cases. Chin Med J 1999; 112 (2): 136-8.

6. Sugie C, Shibamoto Y, Ikeya-Hashizume C, et al. Invasive thymoma: Postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination. J Thorac Oncol 2008; 3 (1): 75-81.

7. Ogawa K, Uno T, Toita T, et al. Postoperative radiotherapy for patients with completely resected thymoma: A multi-institutional, retrospective review of 103 patients. Cancer 2002; 94 (5): 1405-13.

8. Mayer R, Beham-Schmid C, Groell R, et al. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review. Strahlenther Onkol 1999; 175 (6): 271-8.

9. Zhou D, Deng XF, Liu QX, Zheng H, Min JX, Dai JG. The effectiveness of postoperative radiotherapy in patients with completely resected thymoma: A meta-analysis. Ann Thorac Surg 2016; 101 (1): 305-10.

10. Mangi AA, Wain JC, Donahue DM, Grillo HC, Mathisen DJ, Wright CD. Adjuvant radiation of stage III thymoma: Is it necessary? Ann Thorac Surg 2005; 79 (6): 1834-9.

11. Mangi AA, Wright CD, Allan JS, et al. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 2002; 74 (4): 1033-7.

12. Rena O, Papalia E, Oliaro A, et al. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma? Eur J Cardiothorac Surg 2007; 31 (1): 109-13.

13. Yokoi K, Matsuguma H, Nakahara R, et al. Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol 2007; 2 (1): 73-8.

14. Nakagawa K, Yokoi K, Nakajima J, et al. Is Thymomectomy alone appropriate for stage I (T1N0M0) thymoma? Results of a propensity-score analysis. Ann Thorac Surg 2016; 101 (2): 520-6.

15. Wright CD. Management of thymomas. Crit Rev Oncol Hematol 2008;65(2):109-20.

16. Curran WJ, Kornstein MJ, Brooks JJ, Turrisi AT. Invasive thymoma: The role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol 1988; 6 (11): 1722-7.

17. Monden Y, Nakahara K, Iioka S, et al. Recurrence of thymoma: Clinicopathological features, therapy, and prognosis. Ann Thorac Surg 1985; 39 (2): 165-9.

18. Fernandes AT, Shinohara ET, Guo G, et al. The role of radiation therapy in malignant thymoma: A surveillance, epidemiology, and end results database analysis. J Thorac Oncol 2010; 5 (9): 1454-60.

19. Omasa M, Date H, Sozu T, et al. Postoperative radiotherapy is effective for thymic carcinoma but not for thymoma in stage II and III thymic epithelial tumors: The Japanese Association for Research on the Thymus Database Study. Cancer 2015; 121 (7): 1008-16.

20. Patel S, Macdonald OK, Nagda S, Bittner N, Suntharalingam M. Evaluation of the role of radiation therapy in the management of malignant thymoma. Int J Radiat Oncol Biol Phys 2012; 82 (5): 1797-801.

21. Lim YJ, Kim HJ, Wu HG. Role of postoperative radiotherapy in nonlocalized thymoma: Propensity-matched analysis of surveillance, epidemiology, and end results database. J Thorac Oncol 2015; 10 (9): 1357-63.

22. Masaoka A. Staging system of thymoma. J Thorac Oncol 2010; 5 (10 Suppl 4): S304-12.

23. Detterbeck FC, Stratton K, Giroux D, 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; 9 (9 Suppl 2): S65-72.

24. Kondo K, Yoshizawa K, Tsuyuguchi M, et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004; 77 (4): 1183-8.

25. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31 (5): 1341-6.

26. Jackson MW, Palma DA, Camidge DR, et al. The Impact of postoperative radiotherapy thymoma thymic carcinoma. J Thorac Oncol 2017; 12 (4): 734-44.

27. Rimner A, Yao X, Huang J, et al. Postoperative radiation therapy is associated with longer overall survival in completely resected stage II and III thymoma - an analysis of the International Thymic Malignancies Interest Group Retrospective Database. J Thorac Oncol 2016; 11 (10): 1785-92.

28. Lombe D C and B Jeremic. A Review of the Place and Role of Radiotherapy in Thymoma. Clin Lung Cancer 2015; 16 (6): 406-12.

29. Eralp Y, Aydiner A, Kizir A, KaytanE, Oral EN, Topuz E. Resectable thymoma: Treatment outcome and prognostic factors in the late adolescent and adult age group. Cancer Invest 2003; 21 (5): 737-43.

30. Sandri A, Cusumano G, Lococo F, et al. Long-term results after treatment for recurrent thymoma: A multicenter analysis. J Thorac Oncol 2014; 9 (12): 1796-804.

31. Demirci S, Turhan K, Ozsan N, et al. Prognostic factors for survival in patients with thymic epithelial tumors. Thorac Cardiovasc Surg 2011; 59 (3): 153-7.

32. Lu CF, Yu L, Jing Y, Zhang YF, Ke J. Value of adjuvant radiotherapy for thymoma with myasthenia gravis after extended thymectomy. Chin Med J (Engl) 2018; 131 (8): 927-32.

33. Sperling B, Marschall J, Kennedy R, Pahwa P, Chibbar R. Thymoma: A review of the clinical and pathological findings in 65 cases. Can J Surg 2003; 46 (1): 37-42.

34. Girard N, Ruffini E, Marx A, Faivre-Finn C, Peters S. Thymic epithelial tumours: ESMO Clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (Suppl 5): v40-55.

35. Cowen D, Richaud P, Mornex F, et al. Thymoma: Results of a multicentric retrospective series of 149 nonmetastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 1995; 34 (1): 9-16.

36. Perez CBL (ed). Principles and Practice of Radiation Oncology. 6th ed. Philedelphia; Lippincott Williams and Wilkins 2013; 981.

37. Chen YD, Feng QF, Lu HZ, et al. Role of adjuvant radiotherapy for stage II thymoma after complete tumor resection. Int J Radiat Oncol Biol Phys 2010; 78 (5): 1400-6.

38. Fan C, Feng Q, Chen Y, et al. Postoperative radiotherapy for completely resected Masaoka stage III thymoma: A retrospective study of 65 cases from a single institution. Radiat Oncol 2013; 8 (2): 199.

39. Kim ES, Putnam JB, Komaki R, et al. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: Final report. Lung Cancer 2004; 44 (3): 369-79.