Erweiterte Resektionsverfahren bei lokal fortgeschrittenen Tumoren des Thymus im Stadium III

Zusammenfassung

Die Therapie lokal fortgeschrittener Tumoren des Thymus bedarf einer differenzierten Diagnostik und multimodalen Vorgehensweise, bestehend aus Operation, Radio- und/oder Chemotherapie. Im Hinblick auf das rezidivfreie Überleben und das Langzeitüberleben stellt auch in diesem Stadium die radikale und vollständige Resektion des Tumors den wichtigsten prognostischen Faktor dar. Das Masaoka-Koga-Stadium III beschreibt das lokal invasive Wachstum von malignen Thymustumoren in die mediastinalen Nachbarstrukturen. Abhängig vom Ausmaß der Tumorinfiltration kann die operative Resektion primär oder nach einer Induktionstherapie durchgeführt werden. In vielen Fällen müssen diese Tumoren jedoch auch als nicht resektabel eingestuft werden, sodass nur eine palliative Radio-/Chemotherapie als Therapieoption bleibt. Vor wenigen Jahren wurde erstmalig eine neue TNM-Klassifikation für maligne Thymustumoren eingeführt, die in vielen Teilen der klassischen Masaoka-Koga-Klassifikation zwar ähnelt, jedoch auch einige therapierelevante Änderungen beinhaltet. So wird hier zwischen den Stadien IIIA und IIIB unterschieden, mit dem Ziel, bei lokal fortgeschrittenen Thymustumoren die Resektabilität differenzierter einschätzen und folglich auch das gesamte Therapiekonzept entsprechend besser planen zu können. Neben Thymus, Thymom, perithymischem Fettgewebe, mediastinaler Pleura (Stadium I) oder Perikard (Stadium II) sollten bei Tumoren des Stadiums III alle infiltrierten Strukturen nach Möglichkeit „en bloc“ entfernt werden. Während bspw. die Lunge, brachiozephale Gefäße oder extraperikardiale Pulmonalgefäße noch reseziert und ggf. rekonstruiert werden können, limitiert die Infiltration der Aorta oder intraperikardialer Pulmonalgefäße häufig eine makroskopisch vollständige Resektion.

Abstract

In the treatment of locally advanced thymic tumours, specific diagnostic testing is required, with a multimodal therapeutic approach consisting of surgery, radio- and/or chemotherapy. The complete resection of the tumour represents the most important prognostic factor with regard to recurrence-free and long-term survival. Local invasive growth of malignant thymic tumours into neighbouring mediastinal structures is classified as Masaoka-Koga stage III. Surgical resection can be performed primarily or after induction therapy, depending on the extent of the tumour. However, in some cases these tumours must be classified as non-resectable, so that only palliative radio-/chemotherapy remains as therapeutic option. TNM classification for malignant thymic tumours has been recently introduced. This resembles the established Masaoka-Koga classification in many aspects, but also includes some therapy-relevant changes. A differentiation is made between stages IIIA and IIIB, with the aim of assessing the resectability of advanced thymic tumours in a more differentiated manner and consequent planning of the therapy concept. Besides the thymus, thymoma, perithymic tissue, mediastinal pleura (stage I) or pericardium (stage II), all infiltrated structures should be removed “en bloc”, if possible in stage III tumours. While the lung, brachiocephalic vessels or extrapericardial pulmonary vessels can still be resected and reconstructed if necessary, infiltration of the aorta or intrapericardial pulmonary vessels often limits macroscopically complete resection.

Schlüsselwörter

Thymom - Thymuskarzinom - Thymektomie - multimodale Therapie

Key words

thymic carcinoma - thymoma - thymectomy - multimodal therapy

Publication History

Article published online:
23 July 2020

• Literatur

• 1 Smit EF. Thymic malignancies. Ann Oncol 2008; 19 (Suppl. 07) vii309-vii312 doi:10.1093/annonc/mdn471
• 2 Detterbeck FC, Parsons AM. Thymic tumors. Ann Thorac Surg 2004; 77: 1860-1869 doi:10.1016/j.athoracsur.2003.10.001
• 3 Detterbeck FC, Zeeshan A. Thymoma: current diagnosis and treatment. Chin Med J (Engl) 2013; 126: 2186-2191
• 4 Lindenmann J, Fink-Neuboeck N, Pichler M. et al. Stage-based treatment for thymoma in due consideration of thymectomy: a single-center experience and comparison with the literature. World J Surg Oncol 2015; 13: 303 doi:10.1186/s12957-015-0718-z
• 5 Ruffini E, Van Raemdonck D, Detterbeck F. et al. Management of thymic tumors: a survey of current practice among members of the European Society of Thoracic Surgeons. J Thorac Oncol 2011; 6: 614-623 doi:10.1097/JTO.0b013e318207cd74
• 6 Thomas CR, Wright CD, Loehrer PJ. Thymoma: state of the art. J Clin Oncol 1999; 17: 2280-2289 doi:10.1200/JCO.1999.17.7.2280
• 7 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-S72 doi:10.1097/JTO.0000000000000290
• 8 Ried M, Rechenmacher M, Dietl B. et al. Therapie von Thymomen und Thymuskarzinomen. best practice onkologie 2017; 12: 206-214 doi:10.1007/s11654-017-0037-7
• 9 Strobel P, Bauer A, Puppe B. et al. Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis. J Clin Oncol 2004; 22: 1501-1509 doi:10.1200/JCO.2004.10.113
• 10 Tomiyama N, Honda O, Tsubamoto M. et al. Anterior mediastinal tumors: diagnostic accuracy of CT and MRI. Eur J Radiol 2009; 69: 280-288 doi:10.1016/j.ejrad.2007.10.002
• 11 Benveniste MF, Rosado-de-Christenson ML, Sabloff BS. et al. Role of imaging in the diagnosis, staging, and treatment of thymoma. Radiographics 2011; 31: 1847-1861 doi:10.1148/rg.317115505
• 12 Ried M, Hnevkovsky S, Neu R. et al. Impact of surgical evaluation of additional cine magnetic resonance imaging for advanced thymoma with infiltration of adjacent structures: the thoracic surgeonʼs view. Thorac Cardiovasc Surg 2017; 65: 244-249 doi:10.1055/s-0036-1583765
• 13 Marom EM. Imaging thymoma. J Thorac Oncol 2010; 5 (10 Suppl. 4): S296-S303 doi:10.1097/JTO.0b013e3181f209ca
• 14 Pettit L, El-Modir A. The role of somatostatin analogues in the treatment of advanced malignant thymomas: case report and review of the literature. Br J Radiol 2011; 84: e7-e10 doi:10.1259/bjr/16436465
• 15 Endo M, Nakagawa K, Ohde Y. et al. Utility of 18FDG-PET for differentiating the grade of malignancy in thymic epithelial tumors. Lung Cancer 2008; 61: 350-355 doi:10.1016/j.lungcan.2008.01.003
• 16 Travis WD. The 2015 WHO classification of lung tumors. Pathologe 2014; 35 (Suppl. 02) S188 doi:10.1007/s00292-014-1974-3
• 17 Venuta F, Anile M, Diso D. et al. Thymoma and thymic carcinoma. Eur J Cardiothorac Surg 2010; 37: 13-25 doi:10.1016/j.ejcts.2009.05.038
• 18 Marx A, Weis CA, Strobel P. [Thymomas]. Pathologe 2016; 37: 412-424 doi:10.1007/s00292-016-0223-3
• 19 Marulli G, Lucchi M, Margaritora S. et al. Surgical treatment of stage III thymic tumors: a multi-institutional review from four Italian centers. Eur J Cardiothorac Surg 2011; 39: e1-e7 doi:10.1016/j.ejcts.2010.11.026
• 20 Travis WD, Brambilla E, Burke AP. et al. WHO Classification of Tumours of the lung, pleura, thymus and heart. Lyon: International Agency for Research on Cancer; 2015
• 21 Ried M, Marx A, Gotz A. et al. State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma. Eur J Cardiothorac Surg 2016; 49: 1545-1552 doi:10.1093/ejcts/ezv426
• 22 Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 2003; 76: 878-884
• 23 Brierley JD, Gospodarowicz MK, Wittekind C. TNM-Klassifikation maligner Tumoren. 8. Aufl.. Weinheim: Wiley-VCH; 2017
• 24 Detterbeck FC, Nicholson AG, Kondo K. et al. The Masaoka-Koga stage classification for thymic malignancies: clarification and definition of terms. J Thorac Oncol 2011; 6 (7 Suppl. 3): S1710-S1716 doi:10.1097/JTO.0b013e31821e8cff
• 25 Ried M, Eicher MM, Neu R. et al. Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival. World J Surg Oncol 2017; 15: 214 doi:10.1186/s12957-017-1283-4
• 26 Detterbeck F, Youssef S, Ruffini E. et al. A review of prognostic factors in thymic malignancies. J Thorac Oncol 2011; 6 (7 Suppl. 3): S1698-S1704 doi:10.1097/JTO.0b013e31821e7b12
• 27 Hwang Y, Park IK, Park S. et al. Lymph node dissection in thymic malignancies: implication of the ITMIG lymph node map, TNM stage classification, and recommendations. J Thorac Oncol 2016; 11: 108-114 doi:10.1016/j.jtho.2015.09.001
• 28 Viti A, Bertolaccini L, Terzi A. What is the role of lymph nodal metastases and lymphadenectomy in the surgical treatment and prognosis of thymic carcinomas and carcinoids?. Interact Cardiovasc Thorac Surg 2014; 19: 1054-1058 doi:10.1093/icvts/ivu281
• 29 Kattach H, Anastasiadis K, Cleuziou J. et al. Transsternal thymectomy for myasthenia gravis: surgical outcome. Ann Thorac Surg 2006; 81: 305-308 doi:10.1016/j.athoracsur.2005.07.050
• 30 Yamada Y, Yoshino I, Nakajima J. et al. Surgical outcomes of patients with stage III thymoma in the Japanese nationwide database. Ann Thorac Surg 2015; 100: 961-967 doi:10.1016/j.athoracsur.2015.04.059
• 31 Falkson CB, Bezjak A, Darling G. et al. The management of thymoma: a systematic review and practice guideline. J Thorac Oncol 2009; 4: 911-919
• 32 Sur RK, Pacella JA, Donde B. et al. Role of radiotherapy in stage III invasive thymomas. S Afr J Surg 1997; 35: 206-209
• 33 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: 1405-1413 doi:10.1002/cncr.10373
• 34 Fernandes AT, Shinohara ET, Guo M. et al. The role of radiation therapy in malignant thymoma: a surveillance, epidemiology, and end results database analysis. J Thorac Oncol 2010; 5: 1454-1460 doi:10.1097/JTO.0b013e3181e8f345
• 35 Uematsu M, Yoshida H, Kondo M. et al. Entire hemithorax irradiation following complete resection in patients with stage II–III invasive thymoma. Int J Radiat Oncol Biol Phys 1996; 35: 357-360 doi:10.1016/0360-3016(96)00086-7
• 36 Liu HC, Chen YJ, Tzen CY. et al. Debulking surgery for advanced thymoma. Eur J Surg Oncol 2006; 32: 1000-1005 doi:10.1016/j.ejso.2006.03.049
• 37 Wei ML, Kang D, Gu L. et al. Chemotherapy for thymic carcinoma and advanced thymoma in adults. Cochrane Database Syst Rev 2013; (08) CD008588 DOI: 10.1002/14651858.CD008588.pub2.
• 38 Song Z, Yu X, Zhang Y. Chemotherapy and prognosis in advanced thymic carcinoma patients. Clinics (Sao Paulo) 2015; 70: 775-780 doi:10.6061/clinics/2015(12)03
• 39 Zhao C, Rajan A. Immune checkpoint inhibitors for treatment of thymic epithelial tumors: how to maximize benefit and optimize risk?. Mediastinum 2019; DOI: 10.21037/med.2019.08.02.
• 40 Wright CD. Extended resections for thymic malignancies. J Thorac Oncol 2010; 5 (10 Suppl. 4): S344-S347 doi:10.1097/JTO.0b013e3181f20eb3
• 41 Regnard JF, Magdeleinat P, Dromer C. et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg 1996; 112: 376-384 doi:10.1016/S0022-5223(96)70265-9
• 42 Ried M, Neu R, Schalke B. et al. Radical surgical resection of advanced thymoma and thymic carcinoma infiltrating the heart or great vessels with cardiopulmonary bypass support. J Cardiothorac Surg 2015; 10: 137 doi:10.1186/s13019-015-0346-2
• 43 Park BJ, Bacchetta M, Bains MS. et al. Surgical management of thoracic malignancies invading the heart or great vessels. Ann Thorac Surg 2004; 78: 1024-1030 doi:10.1016/j.athoracsur.2004.02.043
• 44 Hamaji M, Kojima F, Omasa M. et al. A meta-analysis of debulking surgery versus surgical biopsy for unresectable thymoma. Eur J Cardiothorac Surg 2015; 47: 602-607 doi:10.1093/ejcts/ezu277
• 45 Bae MK, Lee CY, Lee JG. et al. Predictors of recurrence after thymoma resection. Yonsei Med J 2013; 54: 875-882 doi:10.3349/ymj.2013.54.4.875
• 46 Masaoka A, Monden Y, Nakahara K. et al. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981; 48: 2485-2492
• 47 Ahmad U, Yao X, Detterbeck F. et al. Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg 2015; 149: 95-100 101.e1–e2 doi:10.1016/j.jtcvs.2014.09.124
• 48 Ried M, Potzger T, Braune N. et al. Behandlung maligner Tumoren der Pleura. Z Herz-Thorax-Gefäßchir 2012; 26: 259-262 doi:10.1007/s00398-012-0931-9
• 49 Koga K, Matsuno Y, Noguchi M. et al. A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 1994; 44: 359-367 doi:10.1111/j.1440-1827.1994.tb02936.x