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Systemic Therapies in Thymic Malignancies

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Abstract

There are several types of neoplasms that can originate in the thymus gland such as germ cell tumors, lymphomas, or neuroendocrine cancers, but here, we will be discussing systemic treatment of only the most common types, thymoma (T) and thymic carcinoma (TC). These neoplasms are thymic epithelial tumors (TETs) and they form the most common histologic type of thymic neoplasms.

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References

  1. Engels EA. Epidemiology of thymoma and associated malignancies. J Thorac Oncol. 2010;5(10 Suppl 4):S260–5.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rice TW, Blackstone EH. Rarest of a rare disease: challenges in advancing our knowledge of thymic carcinoma. J Thorac Cardiovasc Surg. 2015;149(1):101–2.

    Article  PubMed  Google Scholar 

  3. Detterbeck FC. The international thymic malignancy interest group. J Natl Compr Cancer Netw. 2013;11(5):589–93.

    Google Scholar 

  4. Huang J, Detterbeck FC, Wang Z, Loehrer PJ. Standard outcome measures for thymic malignancies. J Thorac Oncol. 2011;6(7 Suppl 3):S1691–7.

    Article  PubMed  Google Scholar 

  5. Detterbeck FC, Moran C, Huang J, Suster S, Walsh G, Kaiser L, Wick M. Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol. 2011;6(7 Suppl 3):S1730–8.

    Article  PubMed  Google Scholar 

  6. Detterbeck FC, Nicholson AG, Kondo K, Van Schil P, Moran C. The masaoka-koga stage classification for thymic malignancies: classification and definition of terms. J Thorac Oncol. 2011;6(7 Suppl 3):S1710–6.

    Article  PubMed  Google Scholar 

  7. Marom EM, Rosado-de-Christenson ML, Bruzzi JF, Hara M, Sonett JR, Ketai L. Standard report terms for chest computed tomography reports of anterior mediastinal masses suspicious for thymoma. J Thorac Oncol. 2011;6(7 Suppl 3):S1717–23.

    Article  PubMed  Google Scholar 

  8. Detterbeck F, Youssef S, Ruffini E, Okumura M. A review of prognostic factors in thymic malignancies. J Thorac Oncol. 2011;6(7 Suppl 3):S1698–704.

    Article  PubMed  Google Scholar 

  9. Toker A, Sonett J, Zielinski M, Rea F, Tomulescu V, Detterbeck FC. Standard terms, definitions, and policies for minimally invasive resection of thymoma. J Thorac Oncol. 2011;6(7 Suppl 3):S1739–42.

    Article  PubMed  Google Scholar 

  10. Gomez D, Komaki R, Yu J, Ikushima H, Bezjak A. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol. 2011;6(7 Suppl 3):S1743–8.

    Article  PubMed  Google Scholar 

  11. Girard N, Lal R, Wakelee H, Riely GJ, Loehrer PJ. Chemotherapy definitions and policies for thymic malignancies. J Thorac Oncol. 2011;6(7 Suppl 3):S1749–55.

    Article  PubMed  Google Scholar 

  12. Detterbeck FC, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, 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.

    Article  PubMed  Google Scholar 

  13. Nicholson AG, Detterbeck FC, Marino M, Kim J, Stratton K, Giroux D, et al. The IASLC/ITMIG thymic epithelial tumors staging project: proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014;9(9 Suppl 2):S73–80.

    Article  PubMed  Google Scholar 

  14. Kondo K, Van Schil P, Detterbeck FC, Okumura M, Stratton K, Giroux D, et al. The IASLC/ITMIG thymic epithelial tumors staging project: proposals for the N and M components for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014;9(9 Suppl 2):S81–7.

    Article  PubMed  Google Scholar 

  15. Bhora FY, Chen DJ, Detterbeck FC, Asamura H, Falkson C, Filosso PL, et al. The ITMIG/IASLC thymic epithelial tumors staging project: a proposed lymph node map for thymic epithelial tumors in the forthcoming 8th edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014;9(9 Suppl 2):S88–96.

    Article  PubMed  Google Scholar 

  16. Benveniste MF, Korst RJ, Rajan A, Detterbeck FC, Marom EM, International Thymic Malignancy Interest Group. A practical guide from the international thymic malignancy interest group (ITMIG) regarding the radiographic assessment of treatment response of thymic epithelial tumors using modified RECIST criteria. J Thorac Oncol. 2014;9(9 Suppl 2):S119–24.

    Article  PubMed  Google Scholar 

  17. den Bakker MA, Roden AC, Marx A, Marino M. Histologic classification of thymoma: a practical guide for routine cases. J Thorac Oncol. 2014;9(9 Suppl 2):S125–30.

    Article  Google Scholar 

  18. Rajan A, Girard N, Marx A. State of the art of genetic alterations in thymic epithelial tumors. J Thorac Oncol. 2014;9(9 Suppl 2):S131–6.

    Article  PubMed  Google Scholar 

  19. Weksler B, Lu B. Alterations of the immune system in thymic malignancies. J Thorac Oncol. 2014;9(9 Suppl 2):S137–42.

    Article  PubMed  Google Scholar 

  20. Evoli A, Lancaster E. Paraneoplastic disorders in thymoma patients. J Thorac Oncol. 2014;9(9 Suppl 2):S143–7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Carter BW, Tomiyama N, Bhora FY, de Rosado CML, Nakajima J, Boiselle PM. A modern definition of mediastinal compartments. J Thorac Oncol. 2014;9(9 Suppl 2):S97–101.

    Article  PubMed  Google Scholar 

  22. Carter BW, Marom EM, Detterbeck FC. Approaching the patient with an anterior mediastinal mass: a guide for clinicians. J Thorac Oncol. 2014;9(9 Suppl 2):S102–9.

    Article  PubMed  Google Scholar 

  23. Carter BW, Okumura M, Detterbeck FC, Marom EM. Approaching the patient with an anterior mediastinal mass: a guide for radiologists. J Thorac Oncol. 2014;9(9 Suppl 2):S110–8.

    Article  PubMed  Google Scholar 

  24. Girard N, Ruffini E, Marx A, Faivre-Finn C, Peters S, ESMO Guidelines Committee. Thymic epithelial tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2015;26 Suppl 5:v40–55.

    Article  PubMed  Google Scholar 

  25. Korst RJ, Bezjak A, Blackmon S, Choi N, Fidias P, Liu G, et al. Neoadjuvant chemoradiotherapy for locally advanced thymic tumors: a phase II, multi-institutional clinical trial. J Thorac Cardiovasc Surg. 2014;147(1):36–44, 46.e1.

    Article  PubMed  Google Scholar 

  26. Treglia G, Sadeghi R, Giovanella L, Cafarotti S, Filosso P, Lococo F. Is (18)F-FDG PET useful in predicting the WHO grade of malignancy in thymic epithelial tumors? A meta-analysis. Lung Cancer. 2014;86(1):5–13.

    Article  PubMed  Google Scholar 

  27. Lastoria S, Vergara E, Palmieri G, Acampa W, Varrella P, Caracò C, et al. In vivo detection of malignant thymic masses by indium-111-dtpa-d-phe1-octreotide scintigraphy. J Nucl Med. 1998;39(4):634–9.

    CAS  PubMed  Google Scholar 

  28. Guidoccio F, Grosso M, Maccauro M, Orsini F, Perri M, Boni G, et al. Current role of 111in-dtpa-octreotide scintigraphy in diagnosis of thymic masses. Tumori. 2011;97(2):191–5.

    PubMed  Google Scholar 

  29. De Luca S, Fonti R, Palmieri G, Federico P, Del Prete G, Pacelli R, et al. Combined imaging with 18F-FDG-PET/CT and 111in-labeled octreotide SPECT for evaluation of thymic epithelial tumors. Clin Nucl Med. 2013;38(5):354–8.

    Article  PubMed  Google Scholar 

  30. Makis W, McCann K, McEwan AJ. Thymoma treated with 177lu DOTATATE induction and maintenance PRRT. Clin Nucl Med. 2015;40(5):e278–81.

    Article  PubMed  Google Scholar 

  31. Hofman MS, Kong G, Neels OC, Eu P, Hong E, Hicks RJ. High management impact of ga-68 DOTATATE (gatate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours. J Med Imaging Radiat Oncol. 2012;56(1):40–7.

    Article  PubMed  Google Scholar 

  32. Marchevsky AM, Wick MR. Controversies in the pathology of thymoma viewed through the prism of evidence-based pathology. Oncology (Williston Park). 2012;26(10):982–4.

    Google Scholar 

  33. Detterbeck FC. Clinical value of the WHO classification system of thymoma. Ann Thorac Surg. 2006;81(6):2328–34.

    Article  PubMed  Google Scholar 

  34. Okumura M, Ohta M, Tateyama H, Nakagawa K, Matsumura A, Maeda H, et al. The world health organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer. 2002;94(3):624–32.

    Article  PubMed  Google Scholar 

  35. Falkson CB, Bezjak A, Darling G, Gregg R, Malthaner R, Maziak DE, et al. The management of thymoma: a systematic review and practice guideline. J Thorac Oncol. 2009;4(7):911–9.

    Article  PubMed  Google Scholar 

  36. Girard N, Mornex F, Van Houtte P, Cordier JF, van Schil P. Thymoma: a focus on current therapeutic management. J Thorac Oncol. 2009;4(1):119–26.

    Article  PubMed  Google Scholar 

  37. NCCN clinical practice guidelines in oncology. Accessed 31 Oct 2015.

    Google Scholar 

  38. Ruffini E, Detterbeck F, Van Raemdonck D, Rocco G, Thomas P, Weder W, et al. Thymic carcinoma: a cohort study of patients from the European society of thoracic surgeons database. J Thorac Oncol. 2014;9(4):541–8.

    Article  PubMed  Google Scholar 

  39. Weksler B, Pennathur A, Sullivan JL, Nason KS. Resection of thymoma should include nodal sampling. J Thorac Cardiovasc Surg. 2015;149(3):737–42.

    Article  PubMed  Google Scholar 

  40. Yamada Y, Yoshino I, Nakajima J, Miyoshi S, Ohnuki T, Suzuki M, et al. Surgical outcomes of patients with stage III thymoma in the japanese nationwide database. Ann Thorac Surg. 2015;100(3):961–7.

    Article  PubMed  Google Scholar 

  41. Kunitoh H, Tamura T, Shibata T, Takeda K, Katakami N, Nakagawa K, et al. A phase II trial of dose-dense chemotherapy, followed by surgical resection and/or thoracic radiotherapy, in locally advanced thymoma: report of a Japan clinical oncology group trial (JCOG 9606). Br J Cancer. 2010;103(1):6–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hamaji M, Burt BM. Long-term outcomes of surgical and nonsurgical management of stage IV thymoma: a population-based analysis of 282 patients. Semin Thorac Cardiovasc Surg. 2015;27(1):1–3.

    Article  PubMed  Google Scholar 

  43. Hamaji M, Kojima F, Omasa M, Sozu T, Sato T, Chen F, et al. A meta-analysis of debulking surgery versus surgical biopsy for unresectable thymoma. Eur J Cardiothorac Surg. 2015;47(4):602–7.

    Article  PubMed  Google Scholar 

  44. Hishida T, Nomura S, Yano M, Asamura H, Yamashita M, Ohde Y, et al. Long-term outcome and prognostic factors of surgically treated thymic carcinoma: Results of 306 cases from a Japanese nationwide database study. Eur J Cardiothorac Surg. 2016;49(3):835–41.

    Google Scholar 

  45. Wright CD, Choi NC, Wain JC, Mathisen DJ, Lynch TJ, Fidias P. Induction chemoradiotherapy followed by resection for locally advanced masaoka stage III and IVA thymic tumors. Ann Thorac Surg. 2008;85(2):385–9.

    Article  PubMed  Google Scholar 

  46. Safieddine N, Liu G, Cuningham K, Ming T, Hwang D, Brade A, et al. Prognostic factors for cure, recurrence and long-term survival after surgical resection of thymoma. J Thorac Oncol. 2014;9(7):1018–22.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  48. Loehrer PJ, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, Blum R. 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;12(6):1164–8.

    PubMed  Google Scholar 

  49. Kim JH, Kim BH, Kim YW, Park JC, Jung YH, Lee BO, et al. Autoimmune cholangitis in a patient with thymoma. J Gastroenterol Hepatol. 2004;19(11):1324–7.

    Article  PubMed  Google Scholar 

  50. 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;14(3):814–20.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Koizumi T, Takabayashi Y, Yamagishi S, Tsushima K, Takamizawa A, Tsukadaira A, et al. Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol. 2002;25(3):266–8.

    Article  PubMed  Google Scholar 

  54. Okuma Y, Saito M, Hosomi Y, Sakuyama T, Okamura T. Key components of chemotherapy for thymic malignancies: a systematic review and pooled analysis for anthracycline-, carboplatin- or cisplatin-based chemotherapy. J Cancer Res Clin Oncol. 2015;141(2):323–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Liang Y, Padda SK, Riess JW, West RB, Neal JW, Wakelee HA. Pemetrexed in patients with thymic malignancies previously treated with chemotherapy. Lung Cancer. 2015;87(1):34–8.

    Article  PubMed  Google Scholar 

  56. Agatsuma T, Koizumi T, Kanda S, Ito M, Urushihata K, Yamamoto H, et al. Combination chemotherapy with doxorubicin, vincristine, cyclophosphamide, and platinum compounds for advanced thymic carcinoma. J Thorac Oncol. 2011;6(12):2130–4.

    Article  PubMed  Google Scholar 

  57. Palmieri G, Merola G, Federico P, Petillo L, Marino M, Lalle M, et al. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (tets). Ann Oncol. 2010;21(6):1168–72.

    Article  CAS  PubMed  Google Scholar 

  58. Palmieri G, Buonerba C, Ottaviano M, Federico P, Calabrese F, Von Arx C, et al. Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a phase II trial. Future Oncol. 2014;10(14):2141–7.

    Article  CAS  PubMed  Google Scholar 

  59. Furugen M, Sekine I, Tsuta K, Horinouchi H, Nokihara H, Yamamoto N, et al. Combination chemotherapy with carboplatin and paclitaxel for advanced thymic cancer. Jpn J Clin Oncol. 2011;41(8):1013–6.

    Article  PubMed  Google Scholar 

  60. Watanabe N, Umemura S, Niho S, Kirita K, Matsumoto S, Yoh K, et al. Docetaxel for platinum-refractory advanced thymic carcinoma. Jpn J Clin Oncol. 2015;45(7):665–9.

    Article  PubMed  Google Scholar 

  61. Loehrer PJ, Yiannoutsos CT, Dropcho S, Burns M, Helft P, Chiorean EG, Nelson RP. A phase II trial of pemetrexed in patients with recurrent thymoma or thymic carcinoma. ASCO Meet Abstr. 2006;24(18_Suppl):7079.

    Google Scholar 

  62. Kaira K, Naruse I, Imai H, Sunaga N, Hisada T, Motegi M, et al. Dramatic response of S-1 administration to chemorefractory advanced thymic cancer. Chemotherapy. 2015;60(5–6):356–9.

    Article  CAS  Google Scholar 

  63. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med. 1996;334(4):246–54.

    Article  CAS  PubMed  Google Scholar 

  64. Kunz PL, Reidy-Lagunes D, Anthony LB, Bertino EM, Brendtro K, Chan JA, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013;42(4):557–77.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Palmieri G, Lastoria S, Colao A, Vergara E, Varrella P, Biondi E, et al. Successful treatment of a patient with a thymoma and pure red-cell aplasia with octreotide and prednisone. N Engl J Med. 1997;336(4):263–5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  67. Loehrer PJ, 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;22(2):293–9.

    Article  CAS  PubMed  Google Scholar 

  68. Longo F, De Filippis L, Zivi A, Vitolo D, Del Signore E, Gori B, et al. Efficacy and tolerability of long-acting octreotide in the treatment of thymic tumors: results of a pilot trial. Am J Clin Oncol. 2012;35(2):105–9.

    Article  CAS  PubMed  Google Scholar 

  69. Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 lu-dota 0, tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26(13):2124–30.

    Article  CAS  PubMed  Google Scholar 

  70. Vasamiliette J, Hohenberger P, Schoenberg S, Diehl S, Dinter DJ, Marx A, et al. Treatment monitoring with 18F-FDG PET in metastatic thymoma after 90y-dotatoc and selective internal radiation treatment (SIRT). Hell J Nucl Med. 2009;12(3):271–3.

    PubMed  Google Scholar 

  71. Ferone D, van Hagen MP, Kwekkeboom DJ, van Koetsveld PM, Mooy DM, Lichtenauer-Kaligis E, et al. Somatostatin receptor subtypes in human thymoma and inhibition of cell proliferation by octreotide in vitro. J Clin Endocrinol Metab. 2000;85(4):1719–26.

    Article  CAS  PubMed  Google Scholar 

  72. Dancey J. MTOR signaling and drug development in cancer. Nat Rev Clin Oncol. 2010;7(4):209–19.

    Article  CAS  PubMed  Google Scholar 

  73. Wheler J, Hong D, Swisher SG, Falchook G, Tsimberidou AM, Helgason T, et al. Thymoma patients treated in a phase I clinic at MD Anderson cancer center: responses to mtor inhibitors and molecular analyses. Oncotarget. 2013;4(6):890–8.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Zucali PA, De Pas TM, Palmieri G, Favaretto AG, Chella A, Tiseo M, et al. Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy. ASCO Meet Abstr. 2014;32(15_Suppl):7527.

    Google Scholar 

  75. Kossai M, Duchemann B, Boutros C, Caramella C, Hollebecque A, Angevin E, et al. Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development programs (phase I trials) at gustave roussy. Lung Cancer. 2015;89(3):306–10.

    Article  CAS  PubMed  Google Scholar 

  76. O’Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003;101(9):3597–605.

    Article  PubMed  CAS  Google Scholar 

  77. Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, et al. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015;16(2):177–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Ströbel P, Bargou R, Wolff A, Spitzer D, Manegold C, Dimitrakopoulou-Strauss A, et al. Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. Br J Cancer. 2010;103(2):196–200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Girard N, Teruya-Feldstein J, Payabyab EC, Riely GJ, Rusch VW, Kris MG, Zakowski MF. Insulin-like growth factor-1 receptor expression in thymic malignancies. J Thorac Oncol. 2010;5(9):1439–46.

    Article  PubMed  Google Scholar 

  80. Petrini I, Zucali PA, Lee HS, Pineda MA, Meltzer PS, Walter-Rodriguez B, et al. Expression and mutational status of c-kit in thymic epithelial tumors. J Thorac Oncol. 2010;5(9):1447–53.

    Article  PubMed  Google Scholar 

  81. Simonelli M, Zucali PA, Suter MB, Lorenzi E, Rubino L, Fatuzzo G, et al. Targeted therapy for thymic epithelial tumors: a new horizon? Review of the literature and two cases reports. Future Oncol. 2015;11(8):1223–32.

    Article  CAS  PubMed  Google Scholar 

  82. Rajan A, Carter CA, Berman A, Cao L, Kelly RJ, Thomas A, et al. Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial. Lancet Oncol. 2014;15(2):191–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Thomas A, Rajan A, Szabo E, Tomita Y, Carter CA, Scepura B, et al. A phase I/II trial of belinostat in combination with cisplatin, doxorubicin, and cyclophosphamide in thymic epithelial tumors: a clinical and translational study. Clin Cancer Res. 2014;20(21):5392–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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;29(15):2052–9.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Salter JT, Lewis D, Yiannoutsos C, Loehrer PJ, Risley L, Chiorean EG. Imatinib for the treatment of thymic carcinoma. ASCO Meet Abstr. 2008;26(15_Suppl):8116.

    Google Scholar 

  86. Giaccone G, Smit EF, van Groeningen C, Hogedoorn PC. Phase II study of imatinib in patients with WHO B3 and C thymomas. ASCO Meet Abstr. 2008;26(15_Suppl):14665.

    Google Scholar 

  87. Palmieri G, Buonerba C, Federico P, Formisano L, Nappi L, Di Lorenzo G, et al. Everolimus plus long-acting somatostatin analogs in thymic epithelial malignancies. World J Clin Oncol. 2012;3(7):111–5.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Hagemann IS, Govindan R, Javidan-Nejad C, Pfeifer JD, Cottrell CE. Stabilization of disease after targeted therapy in a thymic carcinoma with KIT mutation detected by clinical next-generation sequencing. J Thorac Oncol. 2014;9(2):e12–6.

    Article  PubMed  Google Scholar 

  89. Lim SH, Lee JY, Sun JM, Kim KM, Ahn JS, Ahn MJ, Park K. A new KIT gene mutation in thymic cancer and a promising response to imatinib. J Thorac Oncol. 2013;8(10):e91–2.

    Article  PubMed  Google Scholar 

  90. Buti S, Donini M, Sergio P, Garagnani L, Schirosi L, Passalacqua R, Rossi G. Impressive response with imatinib in a heavily pretreated patient with metastatic c-kit mutated thymic carcinoma. J Clin Oncol. 2011;29(33):e803–5.

    Article  PubMed  Google Scholar 

  91. Katsuya Y, Fujita Y, Horinouchi H, Ohe Y, Watanabe S, Tsuta K. Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer. 2015;88(2):154–9.

    Article  PubMed  Google Scholar 

  92. Marx A, Weis CA. Sunitinib in thymic carcinoma: enigmas still unresolved. Lancet Oncol. 2015;16(2):124–5.

    Article  PubMed  Google Scholar 

  93. Kurup A, Burns M, Dropcho S, Pao W, Loehrer PJ. Phase II study of gefitinib treatment in advanced thymic malignancies. ASCO Meet Abstr. 2005;23(16_Suppl):7068.

    Google Scholar 

  94. Bedano PM, Perkins S, Burns M, Kessler K, Nelson R, Schneider BP, et al. A phase II trial of erlotinib plus bevacizumab in patients with recurrent thymoma or thymic carcinoma. ASCO Meet Abstr. 2008;26(15_Suppl):19087.

    Google Scholar 

  95. Gubens MA, Burns M, Perkins SM, Pedro-Salcedo MS, Althouse SK, Loehrer PJ, Wakelee HA. A phase II study of saracatinib (AZD0530), a src inhibitor, administered orally daily to patients with advanced thymic malignancies. Lung Cancer. 2015;89(1):57–60.

    Article  PubMed  Google Scholar 

  96. Tumours of the thymus. In: Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC, editors. World Health Organization Classification of Tumours: tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  98. Rea F, Sartori F, Loy M, Calabrò F, Fornasiero A, Daniele O, Altavilla G. Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg. 1993;106(3):543–9.

    CAS  PubMed  Google Scholar 

  99. 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;129(2):100–4.

    Article  CAS  PubMed  Google Scholar 

  100. 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;44(3):369–79.

    Article  PubMed  Google Scholar 

  101. Park S, Ahn MJ, Ahn JS, Sun JM, Shim YM, Kim J, et al. A prospective phase II trial of induction chemotherapy with docetaxel/cisplatin for masaoka stage III/IV thymic epithelial tumors. J Thorac Oncol. 2013;8(7):959–66.

    Article  CAS  PubMed  Google Scholar 

  102. Kawasaki H, Taira N, Ichi T, Yohena T, Kawabata T, Ishikawa K. Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide followed by surgery for thymic carcinoma. Eur J Surg Oncol. 2014;40(9):1151–5.

    Article  CAS  PubMed  Google Scholar 

  103. Hirai F, Yamanaka T, Taguchi K, Daga H, Ono A, Tanaka K, et al. A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L. Ann Oncol. 2015;26(2):363–8.

    Article  PubMed  Google Scholar 

  104. Igawa S, Murakami H, Takahashi T, Nakamura Y, Tsuya A, Naito T, et al. Efficacy of chemotherapy with carboplatin and paclitaxel for unresectable thymic carcinoma. Lung Cancer. 2010;67(2):194–7.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  106. Kunitoh H, Tamura T, Shibata T, Nakagawa K, Takeda K, Nishiwaki Y, et al. A phase-ii trial of dose-dense chemotherapy in patients with disseminated thymoma: report of a Japan clinical oncology group trial (JCOG 9605). Br J Cancer. 2009;101(9):1549–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Tamiya A, Matsumura A, Tsuji T, Morimoto M, Asami K, Okishio K, et al. A pilot study of cisplatin and etoposide with and without radiotherapy for advanced malignant thymoma. Anticancer Res. 2014;34(4):2023–7.

    CAS  PubMed  Google Scholar 

  108. Highley MS, Underhill CR, Parnis FX, Karapetis C, Rankin E, Dussek J, et al. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol. 1999;17(9):2737–44.

    CAS  PubMed  Google Scholar 

  109. Yoh K, Goto K, Ishii G, Niho S, Ohmatsu H, Kubota K, et al. Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide is an effective treatment for advanced thymic carcinoma. Cancer. 2003;98(5):926–31.

    Article  CAS  PubMed  Google Scholar 

  110. Okuma Y, Hosomi Y, Takagi Y, Iguchi M, Okamura T, Shibuya M. Cisplatin and irinotecan combination chemotherapy for advanced thymic carcinoma: evaluation of efficacy and toxicity. Lung Cancer. 2011;74(3):492–6.

    Article  PubMed  Google Scholar 

  111. Komatsu Y, Koizumi T, Tanabe T, Hatayama O, Yasuo M, Okada M, et al. Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma – three cases. Anticancer Res. 2006;26(6C):4851–5.

    CAS  PubMed  Google Scholar 

  112. Watanabe K, Shinkai M, Goto H, Yoshikawa S, Yamaguchi N, Hara Y, et al. Chemotherapy with carboplatin and paclitaxel after failure of primary chemotherapy for advanced thymic carcinoma. A report of three cases and review of the literature. Tumori. 2013;99(4):e172–6.

    PubMed  Google Scholar 

  113. Song Z, Zhang Y. Outcomes after surgical resection of thymic carcinoma: a study from a single tertiary referral centre. Eur J Surg Oncol. 2014;40(11):1523–7.

    Article  CAS  PubMed  Google Scholar 

  114. Kanda S, Koizumi T, Komatsu Y, Yoshikawa S, Okada M, Hatayama O, et al. Second-line chemotherapy of platinum compound plus CPT-11 following ADOC chemotherapy in advanced thymic carcinoma: analysis of seven cases. Anticancer Res. 2007;27(4C):3005–8.

    CAS  PubMed  Google Scholar 

  115. Koizumi T, Agatsuma T, Ichiyama T, Yokoyama T, Ushiki A, Komatsu Y, et al. Salvage chemotherapy with amrubicin and platinum for relapsed thymic carcinoma: experience in six cases. Med Oncol. 2010;27(2):392–6.

    Article  PubMed  Google Scholar 

  116. Hirai F, Seto T, Yamanaka T, Toyozawa R, Inamasu E, Kojo M, et al. Amrubicin as second-line and beyond treatment for platinum-refractory advanced thymic carcinoma. Jpn J Clin Oncol. 2013;43(10):1018–22.

    Article  PubMed  Google Scholar 

  117. Oshita F, Kasai T, Kurata T, Fukuda M, Yamamoto N, Ohe Y, et al. Intensive chemotherapy with cisplatin, doxorubicin, cyclophosphamide, etoposide and granulocyte colony-stimulating factor for advanced thymoma or thymic cancer: preliminary results. Jpn J Clin Oncol. 1995;25(5):208–12.

    CAS  PubMed  Google Scholar 

  118. Grassin F, Paleiron N, André M, Caliandro R, Bretel JJ, Terrier P, et al. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma. A French experience. J Thorac Oncol. 2010;5(6):893–7.

    Article  PubMed  Google Scholar 

  119. Marchevsky AM, Wick MR, editors. Pathology of the Mediastinum. Cambridge University Press; 2014. p. 271).

    Google Scholar 

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Kaban, K. (2016). Systemic Therapies in Thymic Malignancies. In: Ozyigit, G., Selek, U., Topkan, E. (eds) Principles and Practice of Radiotherapy Techniques in Thoracic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-28761-4_18

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