The role of radiation therapy in the management of primary thymic epithelial neoplasms

Abstract

Therapeutic radiation plays an important role in the management of thymoma and thymic carcinoma. These two tumor types differ substantially in their aggressiveness and prognosis. The most pressing issue in radiotherapy is which thymoma and thymic carcinoma patients need radiation. Given that these are rare cancers, few randomized trials have been published. Controversy remains regarding which patients benefit from adjuvant radiation therapy. Existing literature spans patients treated over nearly 50 years, during which time radiation therapy has evolved from rudimentary 2-dimensional based planning to conformal 3-dimensional planning to yet more conformal dose painting techniques such as intensity-modulated radiation therapy and proton therapy. If the effect of radiation is small and the natural history of a disease long, as is the case for stage I favorable histology thymoma, then differences in techniques and toxicities may have as much of an impact as whether radiation was given or not.

Keywords

Thymoma / thymic carcinoma / post-operative radiation therapy

References

[1] Basse C,Molina TJ.Radiorythmic: phase III, opened, randomized study of postoperative radiotherapy versus surveillance in stage IIb/III of masaoka koga thymoma after complete surgical resection.Clin Lung Cancer2021;22:469-72

[2] Shepherd A,Detterbeck F.Thymic carcinoma management patterns among international thymic malignancy interest group (ITMIG) physicians with consensus from the thymic carcinoma working group.J Thorac Oncol2017;12:745-51 PMCID:PMC5545114

[3] Basse C,Bota S.Multidisciplinary tumor board decision making for postoperative radiotherapy in thymic epithelial tumors: insights from the rythmic prospective cohort.J Thorac Oncol2017;12:1715-22

[4] Kao TN,Lin MW.Induction therapy followed by surgery for advanced thymic tumors.Asian J Surg2020;43:707-8

[5] Conforti F,Vitolo V.Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM).ESMO Open2021;6:100188 PMCID:PMC8193108

[6] Girard N,Marx A,Peters S.ESMO guidelines committeethymic epithelial tumours: esmo clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol2015;26 Suppl 5:v40-55

[7] Imbimbo M,Vitali M.Best practices for the management of thymic epithelial tumors: a position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME).Cancer Treat Rev2018;71:76-87

[8] Rico M,Casares C.GOECP/SEOR radiotherapy guidelines for thymic epithelial tumours.World J Clin Oncol2021;12:195-216 PMCID:PMC8085511

[9] Falkson CB,Darling G.The management of thymoma: a systematic review and practice guideline.J Thorac Oncol2009;4:911-9

[10] Kumar N,Bera A.Thymoma: clinical experience from a tertiary care institute from North India.J Cancer Res Ther2013;9:235-9

[11] Zhang H,Wang M,Zhang D.Postoperative radiotherapy for stage I thymoma: a prospective randomized trial in 29 cases.Chin Med J1999;112:136-8

[12] Gomez D,Yu J,Bezjak A.Radiation therapy definitions and reporting guidelines for thymic malignancies.J Thorac Oncol2011;6:S1743-8

[13] Huang J,Wang Z.Standard outcome measures for thymic malignancies.J Thorac Oncol2010;5:2017-23

[14] Rimner A,Huang J.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 Oncol2016;11:1785-92 PMCID:PMC5257334

[15] Forquer JA,Fakiris AJ,Johnstone PA.Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease.Int J Radiat Oncol Biol Phys2010;76:440-5

[16] Lim YJ,Kim JS.Improved survival with postoperative radiotherapy in thymic carcinoma: a propensity-matched analysis of Surveillance, Epidemiology, and End Results (SEER) database.Lung Cancer2017;108:161-7

[17] Muslim Z,Weber JF.Invasive thymoma - which patients benefit from post-operative radiotherapy?.Asian Cardiovasc Thorac Ann2021;29:935-42

[18] Patel S,Nagda S,Suntharalingam M.Evaluation of the role of radiation therapy in the management of malignant thymoma.Int J Radiat Oncol Biol Phys2012;82:1797-801

[19] Weksler B,Nason KS,Ferson PF.The role of adjuvant radiation therapy for resected stage III thymoma: a population-based study.Ann Thorac Surg2012;93:1822-8; discussion 1828

[20] Wen J,Chen D.Evaluation of the prognostic value of surgery and postoperative radiotherapy for patients with thymic neuroendocrine tumors: a propensity-matched study based on the SEER database.Thorac Cancer2018;9:1603-13 PMCID:PMC6275836

[21] Boothe D,Thorpe C,Hitchcock YJ.Postoperative radiotherapy in locally invasive malignancies of the thymus: patterns of care and survival.J Thorac Oncol2016;11:2218-26

[22] Jackson MW,Camidge DR.The impact of postoperative radiotherapy for thymoma and thymic carcinoma.J Thorac Oncol2017;12:734-44

[23] Kim S,Hsu CH.The role of adjuvant therapy in advanced thymic carcinoma: a national cancer database analysis.Ann Thorac Surg2020;109:1095-103

[24] Hamaji M,Ali SO,Lee HS.A meta-analysis of postoperative radiotherapy for thymic carcinoma.Ann Thorac Surg2017;103:1668-75

[25] Lim YJ,Kim HJ.Survival impact of adjuvant radiation therapy in masaoka stage II to IV thymomas: a systematic review and meta-analysis.Int J Radiat Oncol Biol Phys2016;94:1129-36

[26] Ma J,Huang L.Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies.Onco Targets Ther2016;9:4517-26 PMCID:PMC4966637

[27] Tateishi Y,Namkoong H,Takeda A.Postoperative radiotherapy for completely resected masaoka/masaoka-koga stage II/III thymoma improves overall survival: an updated meta-analysis of 4746 patients.J Thorac Oncol2021;16:677-85

[28] Zhou D,Liu QX,Min JX.The effectiveness of postoperative radiotherapy in patients with completely resected thymoma: a meta-analysis.Ann Thorac Surg2016;101:305-10

[29] Liu Q,Yang F.The role of postoperative radiotherapy for stage I/II/III thymic tumor-results of the ChART retrospective database.J Thorac Dis2016;8:687-95

[30] Song SH,Yu WS.The role of postoperative radiotherapy in stage II and III thymoma: a Korean multicenter database study.J Thorac Dis2020;12:6680-9 PMCID:PMC7711424

[31] Bruni A,Perna M.The role of postoperative radiotherapy for thymomas: a multicentric retrospective evaluation from three Italian centers and review of the literature.J Thorac Dis2020;12:7518-30 PMCID:PMC7797870

[32] Leuzzi G,Ruffini E.Multimodality therapy for locally advanced thymomas: a propensity score-matched cohort study from the European Society of Thoracic Surgeons Database.J Thorac Cardiovasc Surg2016;151:47-57.e1

[33] Tang EK,Chang CC.Prognostic factor of completely resected and pathologic T3 N0 M0 thymic epithelial tumor.Ann Thorac Surg2021;111:1164-73

[34] Tseng YH,Tseng YC.Adjuvant therapy for thymic carcinoma-a decade of experience in a taiwan national teaching hospital.PLoS One2016;11:e0146609 PMCID:PMC4710498

[35] Yan J,Moseley JN.Adjuvant radiotherapy for stages II and III resected thymoma: a single-institutional experience.Am J Clin Oncol2016;39:223-7 PMCID:PMC5199721

[36] Wang Y,Du T,Wu Z.A nomogram predicting recurrence and guiding adjuvant radiation for thymic carcinoma after resection.Ann Thorac Surg2018;106:257-63

[37] Yun JK,Kim HR.A nomogram for predicting recurrence after complete resection for thymic epithelial tumors based on the TNM classification: a multi-institutional retrospective analysis.J Surg Oncol2019;119:1161-9

[38] Lee KH,Ahn YC.Patterns of failure following postoperative radiation therapy based on “tumor bed with margin” for stage II to IV type C thymic epithelial tumor.Int J Radiat Oncol Biol Phys2018;102:1505-13

[39] Wang CL,Lyu CX.Intensity modulated radiation therapy for pleural recurrence of thymoma: a prospective phase 2 study.Int J Radiat Oncol Biol Phys2021;109:775-82

[40] Yang AJ,Byun HK,Lee CG.The role of salvage radiotherapy in recurrent thymoma.Radiat Oncol J2019;37:193-200 PMCID:PMC6790798

[41] Hao XJ,Zhou Z.Prospective study of stereotactic body radiation therapy for thymoma and thymic carcinoma: therapeutic effect and toxicity assessment.Sci Rep2017;7:13549 PMCID:PMC5648828

[42] Barsky AR,Katz SI,Cengel KA.Managing oligoprogressive malignant pleural mesothelioma with stereotactic body radiation therapy.Lung Cancer2021;157:163-4

[43] Kashima J.New histological classification and staging of thymic malignancies: ITMIG consensus statements and the 8th TNM staging system.J Thorac Dis2017;9:3656-8 PMCID:PMC5723884

[44] Kim YJ,Song SY.Elective nodal irradiation as adjuvant radiotherapy for advanced thymomas and thymic carcinomas.Clin Lung Cancer2019;20:e91-6

[45] Chevli N,Farach AM.Adaptive radiation therapy for intact thymoma: an illustrative report.Anticancer Res2021;41:2467-71

[46] Gomez D.Technical advances of radiation therapy for thymic malignancies.J Thorac Oncol2010;5:S336-43

[47] Mercado CE,Simone CB 2nd.Proton therapy for thymic malignancies: multi-institutional patterns-of-care and early clinical outcomes from the proton collaborative group and the university of Florida prospective registries.Acta Oncol2019;58:1036-40

[48] Vogel J,Lin L.Prospective study of proton beam radiation therapy for adjuvant and definitive treatment of thymoma and thymic carcinoma: early response and toxicity assessment.Radiother Oncol2016;118:504-9

[49] Vogel J,Litzky LA,Simone CB 2nd.Predicted rate of secondary malignancies following adjuvant proton versus photon radiation therapy for thymoma.Int J Radiat Oncol Biol Phys2017;99:427-33

[50] Vogel J,Simone CB 2nd.Risk of major cardiac events following adjuvant proton versus photon radiation therapy for patients with thymic malignancies.Acta Oncol2017;56:1060-4

[51] Haefner MF,Bougatf N.Dosimetric comparison of advanced radiotherapy approaches using photon techniques and particle therapy in the postoperative management of thymoma.Acta Oncol2018;57:1713-20

[52] Molitoris JK,Snider JW 3rd.Advances in the use of motion management and image guidance in radiation therapy treatment for lung cancer.J Thorac Dis2018;10:S2437-50 PMCID:PMC6123191

[53] Schild SE.Defining the role of hemithorax irradiation for thymomas is difficult.J Thorac Oncol2008;3:1-2