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Thymic malignancies focusing on systemic treatment

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Abstract

Malignancies originating from thymic epithelial tissue are rare and treatment approach depends on the individual situation. There are no randomized trials that provide evidence of therapy for patients with thymoma and thymic carcinoma. Treatment includes surgery, radiation therapy, and systemic therapy. For early stage tumors, surgery is the treatment of choice. Long-term survival depends on histologic type, presence of invasion, and quality of surgical resection. For locally advanced thymomas and thymic carcinomas, multimodal treatment includes neoadjuvant chemotherapy and adjuvant radiation. Patients with metastatic tumors are mainly treated with palliative chemotherapy. The optimal chemotherapy combination has not yet been established, although platinum-based drug regimes show reasonable response rates. For patients with poor performance status, the somatostatin (SST) analog octreotide with high affinity for SST receptors could be a potential treatment alternative. Small trials showed tumor responses, especially in combination with prednisolone. In the last decade, an effort has been made to establish targeted agents in the treatment of thymomas and thymic carcinomas. Nevertheless, up to now these agents have had only limited activity in this rare malignancy.

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References

  1. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003;105(4):546–551.

    Article  PubMed  CAS  Google Scholar 

  2. Schmidt-Wolf IG, Rockstroh JK, Schuller H, Hirner A, Grohe C, Muller-Hermelink HK, et al. Malignant thymoma: current status of classification and multimodality treatment. Ann Hematol. 2003;82(2):69–76.

    PubMed  CAS  Google Scholar 

  3. Rosai J. Histological typing of tumours of the thymus. 1999; 2nd ed.

  4. Strobel P, Hohenberger P, Marx A. Thymoma and thymic carcinoma: molecular pathology and targeted therapy. J Thorac Oncol. 2010 Oct;5(10 Suppl 4):S286–90.

    Article  PubMed  Google Scholar 

  5. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer. 1981 Dec 1;48(11):2485–92.

    Article  PubMed  CAS  Google Scholar 

  6. Gamondes JP, Balawi A, Greenland T, Adleine P, Mornex JF, Zhang J, et al. Seventeen years of surgical treatment of thymoma: factors influencing survival. Eur J Cardiothorac Surg. 1991;5(3):124–31.

    Article  PubMed  CAS  Google Scholar 

  7. Kim DJ, Yang WI, Choi SS, Kim KD, Chung KY. Prognostic and clinical relevance of the World Health Organization schema for the classification of thymic epithelial tumors: a clinicopathologic study of 108 patients and literature review. Chest. 2005 Mar;127(3):755–61.

    Article  PubMed  Google Scholar 

  8. Souadjian JV, Enriquez P, Silverstein MN, Pepin JM. The spectrum of diseases associated with thymoma. coincidence or syndrome? Arch Intern Med. 1974 Aug;134(2):374–9.

    Article  PubMed  CAS  Google Scholar 

  9. Dessypris EN. The biology of pure red cell aplasia. Semin Hematol. 1991 Oct;28(4):275–84.

    PubMed  CAS  Google Scholar 

  10. Verley JM, Hollmann KH. Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. Cancer. 1985 Mar 1;55(5):1074–86.

    Article  PubMed  CAS  Google Scholar 

  11. Quagliano PV. Thymic carcinoma: case reports and review. J Thorac Imaging. 1996 Winter;11(1):66–74.

    Article  PubMed  CAS  Google Scholar 

  12. Sung YM, Lee KS, Kim BT, Choi JY, Shim YM, Yi CA. 18F-FDG PET/CT of thymic epithelial tumors: usefulness for distinguishing and staging tumor subgroups. J Nucl Med. 2006 Oct;47(10):1628–34.

    PubMed  Google Scholar 

  13. Strobel P, Bauer A, Puppe B, Kraushaar T, Krein A, Toyka K, et al. Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis. J Clin Oncol. 2004 Apr 15;22(8):1501–9.

    Article  PubMed  Google Scholar 

  14. Maggi G, Casadio C, Cavallo A, Cianci R, Molinatti M, Ruffini E. Thymoma: results of 241 operated cases. Ann Thorac Surg. 1991 Jan;51(1):152–6.

    Article  PubMed  CAS  Google Scholar 

  15. 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 (Engl). 1999 Feb;112(2):136–8.

    CAS  Google Scholar 

  16. Singhal S, Shrager JB, Rosenthal DI, LiVolsi VA, Kaiser LR. Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg. 2003 Nov;76(5):1635–41; discussion 1641–2.

    Article  PubMed  Google Scholar 

  17. Ogawa K, Uno T, Toita T, Onishi H, Yoshida H, Kakinohana Y, et al. Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer. 2002 Mar 1;94(5):1405–13.

    Article  PubMed  Google Scholar 

  18. Thomas CR, Wright CD, Loehrer PJ. Thymoma: state of the art. J Clin Oncol. 1999 Jul;17(7):2280–9.

    PubMed  CAS  Google Scholar 

  19. Mangi AA, Wright CD, Allan JS, Wain JC, Donahue DM, Grillo HC, et al. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg. 2002 Oct;74(4):1033–7.

    Article  PubMed  Google Scholar 

  20. Ariaratnam LS, Kalnicki S, Mincer F, Botstein C. The management of malignant thymona with radiation therapy. Int J Radiat Oncol Biol Phys. 1979 Jan;5(1):77–80.

    Article  PubMed  CAS  Google Scholar 

  21. Penn CR, Hope-Stone HF. The role of radiotherapy in the management of malignant thymoma. Br J Surg. 1972 Jul;59(7):533–9.

    Article  PubMed  CAS  Google Scholar 

  22. Curran WJ, Jr, Kornstein MJ, Brooks JJ, Turrisi AT, 3rd. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol. 1988 Nov;6(11):1722–7.

    PubMed  Google Scholar 

  23. Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg. 2003 Sep;76(3):878–84; discussion 884–5.

    Article  PubMed  Google Scholar 

  24. Loehrer PJ S, Chen M, Kim K, Aisner SC, Einhorn LH, Livingston R, et al. Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial. J Clin Oncol. 1997 Sep;15(9):3093–9.

    PubMed  CAS  Google Scholar 

  25. Macchiarini P, Chella A, Ducci F, Rossi B, Testi C, Bevilacqua G, et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer. 1991 Aug 15;68(4):706–13.

    Article  PubMed  CAS  Google Scholar 

  26. Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, 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 Jun;44(3):369–79.

    Article  PubMed  Google Scholar 

  27. Fornasiero A, Daniele O, Ghiotto C, Piazza M, Fiore-Donati L, Calabro F, et al. Chemotherapy for invasive thymoma. A 13-year experience. Cancer. 1991 Jul 1;68(1):30–3.

    Article  PubMed  CAS  Google Scholar 

  28. Berruti A, Borasio P, Gerbino A, Gorzegno G, Moschini T, Tampellini M, et al. Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience. Br J Cancer. 1999 Nov;81(5):841–5.

    Article  PubMed  CAS  Google Scholar 

  29. Rea F, Sartori F, Loy M, Calabro F, Fornasiero A, Daniele O, et al. Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg. 1993 Sep;106(3):543–9.

    PubMed  CAS  Google Scholar 

  30. Loehrer PJ S, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, et al. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol. 1994 Jun;12(6):1164–8.

    PubMed  Google Scholar 

  31. Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, 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 Jun;44(3):369–79.

    Article  PubMed  Google Scholar 

  32. Shin DM, Walsh GL, Komaki R, Putnam JB, Nesbitt J, Ro JY, et al. A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med. 1998 Jul 15;129(2):100–4.

    PubMed  CAS  Google Scholar 

  33. Loehrer PJ S, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR, Jr, et al. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer. 2001 Jun 1;91(11):2010–5.

    Article  PubMed  CAS  Google Scholar 

  34. Giaccone G, Ardizzoni A, Kirkpatrick A, Clerico M, Sahmoud T, van Zandwijk N. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 1996 Mar;14(3):814–20.

    PubMed  CAS  Google Scholar 

  35. Macchiarini P, Chella A, Ducci F, Rossi B, Testi C, Bevilacqua G, et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer. 1991 Aug 15;68(4):706–13.

    Article  PubMed  CAS  Google Scholar 

  36. Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, et al. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20;29(15):2060–5.

    Article  PubMed  CAS  Google Scholar 

  37. Loehrer PJ, Yiannoutsos CT, Dropcho S, Burns M, Helft P, Chiorean EG, et al. A phase II trial of pemetrexed in patients with recurrent thymoma or thymic carcinoma. J Clin Oncol. 2006;24:18s.

    Article  Google Scholar 

  38. Reubi JC, Waser B, Horisberger U, Krenning E, Lamberts SW, Gebbers JO, et al. In vitro autoradiographic and in vivo scintigraphic localization of somatostatin receptors in human lymphatic tissue. Blood. 1993 Oct 1;82(7):2143–51.

    PubMed  CAS  Google Scholar 

  39. Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993 Aug;20(8):716–31.

    Article  PubMed  CAS  Google Scholar 

  40. Ferone D, van Hagen PM, van Koetsveld PM, Zuijderwijk J, Mooy DM, Lichtenauer-Kaligis EG, et al. In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells. Endocrinology. 1999 Jan;140(1):373–80.

    Article  PubMed  CAS  Google Scholar 

  41. Palmieri G, Montella L, Martignetti A, Muto P, Di Vizio D, De Chiara A, et al. Somatostatin analogs and prednisone in advanced refractory thymic tumors. Cancer. 2002 Mar 1;94(5):1414–20.

    Article  PubMed  CAS  Google Scholar 

  42. Loehrer PJS, Wang W, Johnson DH, Aisner SC, Ettinger DS, Eastern Cooperative Oncology Group Phase II Trial. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol. 2004 Jan 15;22(2):293–9.

  43. Schalke B. Treatment of unresectable thymoma with neoadjuvant octreotide LAR. J Clin Oncol. 2010;28 (abstr.13540).

  44. Kurup A, Burns M, Dropcho S, Pao W, Loehrer PJ. Phase II study of gefitinib treatment in advanced thymic malignancies. J Clin Oncol. 2005;23:16s (abstr 7068).

    Google Scholar 

  45. Bedano PM, Perkins S, Burns M. A phase II trial of erlotinib plus bevacizumab in patients with recurrent thymoma or thymic carcinoma. J Clin Oncol. 2008;26:713s (abstr. 19087).

    Google Scholar 

  46. Pan CC, Chen PC, Chiang H. KIT (CD117) is frequently overexpressed in thymic carcinomas but is absent in thymomas. J Pathol. 2004 Mar;202(3):375–81.

    Article  PubMed  CAS  Google Scholar 

  47. Salter JT, Lewis D, Yiannoutsos PJ. Imatinib for the treatment of thmyic carcinoma. J Clin Oncol 2008;26:452s (abstr. 8116).

    Google Scholar 

  48. Giaccone G, Rajan A, Ruijter R, Smit E, van Groeningen C, Hogendoorn PC. Imatinib mesylate in patients with WHO B3 thymomas and thymic carcinomas. J Thorac Oncol. 2009 Oct;4(10):1270–3.

    Article  PubMed  Google Scholar 

  49. Giaccone G, Rajan A, Berman A, Kelly RJ, Szabo E, Lopez-Chavez A, et al. Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. J Clin Oncol. 2011 May 20;29(15):2052–9.

    Article  PubMed  Google Scholar 

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Acknowledgements

The international thymic malignancy interest group (ITMIG) promotes international collaboration and science for thymic malignancies (www.itmig.org).

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Correspondence to Gudrun Absenger MD.

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Absenger, G., Ploner, F. Thymic malignancies focusing on systemic treatment. memo 6, 9–13 (2013). https://doi.org/10.1007/s12254-013-0069-9

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