Radiotherapy for Thymic Neoplasms
2010; Elsevier BV; Volume: 5; Issue: 10 Linguagem: Inglês
10.1097/jto.0b013e3181f20ec4
ISSN1556-1380
AutoresClifton D. Fuller, Emma H. Ramahi, Noel J. Aherne, Tony Y. Eng, Charles R. Thomas,
Tópico(s)Meningioma and schwannoma management
ResumoThe role of radiotherapy in the treatment of thymoma and thymic carcinoma has been evaluated by many investigators over the past two decades. The low incidence of these neoplasms has limited most published studies to small series spanning long time intervals or population-based studies. The exact indications and protocols for the use of radiotherapy as a part of the multidisciplinary approach to thymoma and thymic carcinoma are still unclear. However, a review of recent literature shows potential benefits for certain patients based on stage and grade of disease as well as the extent of surgical resection. The role of radiotherapy in the treatment of thymoma and thymic carcinoma has been evaluated by many investigators over the past two decades. The low incidence of these neoplasms has limited most published studies to small series spanning long time intervals or population-based studies. The exact indications and protocols for the use of radiotherapy as a part of the multidisciplinary approach to thymoma and thymic carcinoma are still unclear. However, a review of recent literature shows potential benefits for certain patients based on stage and grade of disease as well as the extent of surgical resection. Because of the sensitivity of thymoma and thymic carcinoma to radiation therapy, there is much interest in the role of radiotherapy (RT) in the treatment of these rare neoplasms. Although it is the most common anterior mediastinal compartment neoplasm (Figure 1),1Engles EA Pfeiffer RM Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies.Int J Cancer. 2003; 105: 546-551Crossref PubMed Scopus (338) Google Scholar low incidence and indolent natural history of the disease have made the work of developing definitive recommendations for RT in the multidisciplinary approach to the treatment of thymic neoplasms difficult. In addition, the rapid advances in the delivery of RT make it difficult to evaluate the potential benefit of current treatment practices using data collected over several decades. Currently, no domestic randomized prospective clinical trials evaluating the role of adjuvant RT after complete resection of thymoma or thymic carcinoma have been published. However, retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database as well as multiple small case series show potential for the use of adjuvant RT for the treatment of selected subpopulations of patients with thymoma and thymic carcinoma. Complete surgical resection provides an 82% 7-year survival rate, whereas incomplete resection and biopsy alone are associated with 71 and 26%, respectively.2Maggi G Casadio C Cavallo A et al.Thymoma: results of 241 operated cases.Ann Thorac Surg. 1991; 51: 152-156Abstract Full Text PDF PubMed Scopus (315) Google Scholar Therefore, the mainstay of treatment for thymoma and thymic carcinoma without unresectable/metastatic disease has been en bloc resection of the tumor and adjacent involved structures.3Port J Ginsberg RJ Surgery for thymoma.Chest Surg Clin N Am. 2001; 11: 421-437PubMed Google Scholar There is a potential role for both RT and chemoradiotherapy to prevent recurrence for patients in whom a complete surgical resection is not possible. Some investigators in the late 1980s recommended adjuvant RT for all thymic neoplasms regardless of stage or completeness of resection.4Monden Y Nakahara K Iioka S et al.Recurrence of thymoma: clinicopathological features, therapy, and prognosis.Ann Thorac Surg. 1985; 39: 165-169Abstract Full Text PDF PubMed Scopus (143) Google Scholar, 5Nakahara K Ohno K Hashimoto J et al.Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients.J Thorac Cardiovasc Surg. 1988; 95: 1041-1047PubMed Google Scholar More recent studies have called this practice into question, and current work is focused on the benefit of RT for patients stratified by tumor stage and resection characteristics. Awad et al.6Awad WI Symmans PJ Dussek JE Recurrence of stage I thymoma 32 years after total excision.Ann Thorac Surg. 1998; 66: 2106-2108Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar performed a longitudinal study of patients with Masaoka stage I thymomas (which are completely encapsulated) who underwent complete resection and followed up for 32 years found a 2 to 3% recurrence rate, suggesting that adjuvant RT is unlikely to improve the prognosis in this population of patients. Furthermore, the only randomized prospective trial performed to date, a small (n = 29) series from Peking Union Medical College, demonstrated no survival benefit to RT (88% 10-year survival) compared with surgery alone (92% 10-year overall survival) in Masaoka stage I patients.7Zhang H Lu N Wang M et al.Postoperative radiotherapy for a stage I thymoma: a prospective randomized trial in 29 cases.Chin Med J. 1999; 112: 136-138PubMed Google Scholar Several other investigators also have data to suggest adjuvant RT provides no benefit for localized disease but potentially benefits Masaoka stage II and III8Gamondes JP Balawi A Greenland T et al.Seventeen years of surgical treatment of thymoma: factors influencing survival.Eur J Cardiothorac Surg. 1991; 5: 124-131Crossref PubMed Scopus (89) Google Scholar, 9Regnard JF Fourquier P Levasseur P Results and prognostic factors in resections of primary tracheal tumors: a multicenter retrospective study. The French Society of Cardiovascular Surgery.J Thorac Cardiovasc Surg. 1996; 111 (discussion 813–814.): 808-813Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 10Cowen D Richaud P Mornex F et al.Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer.Radiother Oncol. 1995; 34: 9-16Abstract Full Text PDF PubMed Scopus (123) Google Scholar, 11Wilkens EW Grillo HC Scannell JG et al.Role of staging in prognosis and management of thymoma.Ann Thorac Surg. 1991; 51: 888-892Abstract Full Text PDF PubMed Scopus (137) Google Scholar, 12Kaiser LR Martini N Clinical management of thymomas: the Memorial Sloan-Kettering Cancer Center experience.in: Martini N Vogt-Moykopf I Thoracic Surgery: Frontiers and Uncommon Neoplasms. Vol. 5. Mosby, St. Louis, MO1989: 176-183Google Scholar, 13Housman DM Smith BD Detterbeck FC et al.The role of radiation therapy in malignant thymomas: a population-based study.Int J Rad Oncol Biol Phys. 2006; 66: S150Abstract Full Text Full Text PDF Google Scholar and patients receiving incomplete resections.8Gamondes JP Balawi A Greenland T et al.Seventeen years of surgical treatment of thymoma: factors influencing survival.Eur J Cardiothorac Surg. 1991; 5: 124-131Crossref PubMed Scopus (89) Google Scholar, 10Cowen D Richaud P Mornex F et al.Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer.Radiother Oncol. 1995; 34: 9-16Abstract Full Text PDF PubMed Scopus (123) Google Scholar, 14Kondo K Monden Y Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.Ann Thorac Surg. 2003; 76 (discussion 884–885.): 878-884Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar In higher stage disease, the benefit of adjuvant RT may be more readily detectable. A population-based domestic survival analysis of malignant thymoma analyzing the SEER registry data (n = 599) revealed significant overall survival benefit from adjuvant RT for a population comparable with Masaoka stage II.13Housman DM Smith BD Detterbeck FC et al.The role of radiation therapy in malignant thymomas: a population-based study.Int J Rad Oncol Biol Phys. 2006; 66: S150Abstract Full Text Full Text PDF Google Scholar In a more recent retrospective study using SEER registry data (n = 901), adjuvant RT provided no advantage in terms of overall survival for patients with Masaoka stage I thymoma and thymic carcinoma; however, significant increase in overall survival was seen in patients with Masaoka stage II and III disease, especially when surgery was nonextirpative.15Forquer JA Rong N Fakiris AJ et al.Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease.Int J Radiat Oncol Biol Phys. 2010; 76: 440-445Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar However, the SEER registry data included is not coded for surgical resection status (R0/R1/R2), use of chemotherapy, consistent histopathologic criteria,13Housman DM Smith BD Detterbeck FC et al.The role of radiation therapy in malignant thymomas: a population-based study.Int J Rad Oncol Biol Phys. 2006; 66: S150Abstract Full Text Full Text PDF Google Scholar radiation dose, number of fractions, or elapsed days in the treatment course.15Forquer JA Rong N Fakiris AJ et al.Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease.Int J Radiat Oncol Biol Phys. 2010; 76: 440-445Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar This limits the further refinement of selection criteria that are possible from SEER data. A recent retrospective study (n = 175) has also corroborated the data from these population-based studies (Table 1).16Zhu G He S Fu X et al.Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.Int J Radiat Oncol Biol Phys. 2004; 60: 1113-1119Abstract Full Text Full Text PDF PubMed Scopus (57) Google ScholarTABLE 1Selected Studies Detailing Radiotherapy Outcomes for ThymomaAuthorMasaoka StageNIncluded RT RegimensDose Specification (Gy)5-Year Local Control (%)5-Year Survival Rate (%)Cowen et al.10Cowen D Richaud P Mornex F et al.Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer.Radiother Oncol. 1995; 34: 9-16Abstract Full Text PDF PubMed Scopus (123) Google ScholarPreoperative/postoperative ± chemotherapy22–50 (preoperative)78.5 series59.5 DFS30–70 (postoperative)I13100II4698III5869IVa3259Curran et al.18Curran Jr, WJ Kornstein MJ Brooks JJ et al.Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.J Clin Oncol. 1988; 6: 1722-1727PubMed Google ScholarI43Postoperative (II–IV)32–60II21II–III 79 if R1/R253III36100 if R053IV3Forquer et al.15Forquer JA Rong N Fakiris AJ et al.Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease.Int J Radiat Oncol Biol Phys. 2010; 76: 440-445Abstract Full Text Full Text PDF PubMed Scopus (79) Google ScholarPostoperativeNSLocalized179—81Regionalized407—76Haniuda et al.61Haniuda M Morimoto M Nishimura H et al.Adjuvant radiotherapy after complete resection of thymoma.Ann Thorac Surg. 1992; 54: 311-315Abstract Full Text PDF PubMed Scopus (97) Google ScholarPostoperative40–50II7010074III7069Jackson62II–III28Postoperative32–60 (mean 42)6153Kondo and Monden14Postoperative ± chemotherapyNSI55299.1100II24795.998.4III17071.688.7IV4265.770.6 (IVa)52.8 (IVb)Korst et al.27Korst RJ Kansler AL Christos PJ et al.Adjuvant radiotherapy for thymic epithelial tumors: a systematic review and meta-analysis.Ann Thorac Surg. 2009; 87: 1641-1647Abstract Full Text Full Text PDF PubMed Scopus (82) Google ScholarPostoperativeNSII19775–100—III5336–100—Latz et al.63Latz D Schraube P Oppitz U et al.Invasive thymoma: treatment with postoperative radiation therapy.Radiology. 1997; 204: 859-864Crossref PubMed Scopus (64) Google ScholarPostoperative ± chemotherapy10–72 (median 50)II108190III1467IV1930Mornex et al.29Mornex F Resbeut M Richaud P et al.Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer.Int J Radiat Oncol Biol Phys. 1995; 32: 651-659Abstract Full Text PDF PubMed Scopus (94) Google ScholarPreoperative/postoperative ± chemotherapy30–70 (median 50)IIIa218664IIIb3759 (IIIb + IVa)39IVa32Myojin et al.31Myojin M Choi NC Wright CD et al.Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study.Int J Radiat Oncol Biol Phys. 2000; 46: 927-933Abstract Full Text Full Text PDF PubMed Scopus (101) Google ScholarIII32Preoperative/postoperative40–606371Nakahara et al.5Nakahara K Ohno K Hashimoto J et al.Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients.J Thorac Cardiovasc Surg. 1988; 95: 1041-1047PubMed Google ScholarPostoperative30–50I45—100II33—91.5III48—87.8IV15—46.6Pollack et al.64Pollack A Komaki R Cox JD et al.Thymoma: treatment and prognosis.Int J Radiat Oncol Biol Phys. 1992; 23: 1037-1043Abstract Full Text PDF PubMed Scopus (91) Google ScholarPostoperative/definitive50 (median)59 (overall)I1174II871III1050IV729Singhal et al.20Singhal SJ, S Rosenthal DI LiVolsi VA et al.Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation.Ann Thorac Surg. 2003; 76: 1635-1642Abstract Full Text Full Text PDF PubMed Scopus (142) Google ScholarPostoperative45–55I3100—IIa10100—Iib1090—Urgesi et al.17Urgesi A Monetti U Rossi G et al.Role of radiation therapy in locally advanced thymoma.Radiother Oncol. 1990; 19: 273-280Abstract Full Text PDF PubMed Scopus (82) Google ScholarPreoperative/postoperative39.6–60III5985–9078Utsumi et al.28Utsumi T Shiono H Kadota Y et al.Postoperative radiation therapy after complete resection of thymoma has little impact on survival.Cancer. 2009; 115: 5413-5420Crossref PubMed Scopus (67) Google ScholarPostoperative10–50 (mean 39.3)I31—77.3 (10-yr OS)II43—85 (10-yr OS)III53—79.9 (10-yr OS)IV7—62.5 (5-yr OS)Zhu et al.16Zhu G He S Fu X et al.Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.Int J Radiat Oncol Biol Phys. 2004; 60: 1113-1119Abstract Full Text Full Text PDF PubMed Scopus (57) Google ScholarPostoperative45–65I47(60–65 if R1/R2; 50–55 if R0)96.6II4156.496III4142.777.8IVa3221.656.6IVb935.6DFS, disease-free survival; OS, overall survival. Open table in a new tab DFS, disease-free survival; OS, overall survival. In addition, there are data from smaller, mostly institutional series to suggest survival benefit via reduction of recurrences both in the field of radiation and secondary distant progression with adjuvant RT.2Maggi G Casadio C Cavallo A et al.Thymoma: results of 241 operated cases.Ann Thorac Surg. 1991; 51: 152-156Abstract Full Text PDF PubMed Scopus (315) Google Scholar, 17Urgesi A Monetti U Rossi G et al.Role of radiation therapy in locally advanced thymoma.Radiother Oncol. 1990; 19: 273-280Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 18Curran Jr, WJ Kornstein MJ Brooks JJ et al.Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.J Clin Oncol. 1988; 6: 1722-1727PubMed Google Scholar, 19Ciernik IF Meier U Lutolf UM Prognostic factors and outcome of incompletely resected invasive thymoma following radiation therapy.J Clin Oncol. 1994; 12: 1484-1490Crossref PubMed Scopus (87) Google Scholar Although not statistically significant, a study of 68 patients by Curran et al.18Curran Jr, WJ Kornstein MJ Brooks JJ et al.Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.J Clin Oncol. 1988; 6: 1722-1727PubMed Google Scholar showed that local recurrence reaches 47% at 5 years in patients with stage II and III disease after an R0 resection without adjuvant RT, whereas no recurrence was noted after the addition on adjuvant RT. Likewise, of the 33 patients receiving adjuvant RT, Urgesi et al.17Urgesi A Monetti U Rossi G et al.Role of radiation therapy in locally advanced thymoma.Radiother Oncol. 1990; 19: 273-280Abstract Full Text PDF PubMed Scopus (82) Google Scholar showed no in field recurrences and three out of field recurrences, lending credence to the efficacy of local control with adjuvant management. However, several contrasting datasets have also been presented, with countervailing findings regarding RT utilization. In one of the largest series to date, Kondo and Monden14Kondo K Monden Y Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.Ann Thorac Surg. 2003; 76 (discussion 884–885.): 878-884Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar presented international report of >1000 pooled thymoma patients, including 247 stage II cases, showing no difference between surgery alone and adjuvant RT. A smaller domestic report at the University of Pennsylvania of 167 patients undergoing surgical resection of thymoma showed no benefit from adjuvant RT in margin negative stage II disease.20Singhal SJ, S Rosenthal DI LiVolsi VA et al.Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation.Ann Thorac Surg. 2003; 76: 1635-1642Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar Several other studies showed no decrease in local or distant recurrence after R0 resection for stage III thymoma with adjuvant RT,21Blumberg D Port JL Weksler B et al.Thymoma: a multivariate analysis of factors predicting survival.Ann Thorac Surg. 1995; 60 (discussion 914.): 908-913Abstract Full Text PDF PubMed Scopus (305) Google Scholar, 22Haniuda M Miyazawa M Yoshida K et al.Is postoperative radiotherapy for thymoma effective?.Ann Surg. 1996; 224: 219-224Crossref PubMed Scopus (77) Google Scholar, 23Mangi AA Wain JC Donahue DM et al.Adjuvant radiation of stage III thymoma: is it necessary?.Ann Thorac Surg. 2005; 79: 1834-1839Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 24Mangi AA Wright CD Allan JS et al.Adjuvant radiation therapy for stage II thymoma.Ann Thorac Surg. 2002; 74: 1033-1037Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar and Ruffini et al.25Ruffini E Mancuso M Oliaro A et al.Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome.J Thorac Cardiovasc Surg. 1997; 113: 55-63Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar actually showed worse outcomes with the addition of adjuvant RT. Another recent study of 41 thymoma patients actually showed a significantly longer total survival time in patients with stage II disease who did not receive adjuvant RT.26Vassiliou V Tsamandas A Katodritis N et al.The role of postoperative radiotherapy in the management of patients with thymic tumors—a retrospective study.In Vivo. 2009; 5: 843-852Google Scholar Likewise, a meta-analysis published in 2009 by Korst et al.27Korst RJ Kansler AL Christos PJ et al.Adjuvant radiotherapy for thymic epithelial tumors: a systematic review and meta-analysis.Ann Thorac Surg. 2009; 87: 1641-1647Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar used data on 592 patients obtained from 13 of 22 retrospective cohort studies and showed no benefit of adjuvant RT on recurrence rates after complete resection of stage II and/or III thymic epithelial tumors. Consequently, the use of radiation remains an area of debate and institutional norms. However, adjuvant RT is widely believed to be the standard of care for residual disease after incomplete resections of stage III and IV disease. Curran et al.18Curran Jr, WJ Kornstein MJ Brooks JJ et al.Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.J Clin Oncol. 1988; 6: 1722-1727PubMed Google Scholar also showed no mediastinal failures after radiation in 26 patients with stage III thymomas and 79% recurrence after 5 years without adjuvant RT. Other studies had similar findings with low mediastinal recurrence after treatment with adjuvant RT.17Urgesi A Monetti U Rossi G et al.Role of radiation therapy in locally advanced thymoma.Radiother Oncol. 1990; 19: 273-280Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 19Ciernik IF Meier U Lutolf UM Prognostic factors and outcome of incompletely resected invasive thymoma following radiation therapy.J Clin Oncol. 1994; 12: 1484-1490Crossref PubMed Scopus (87) Google Scholar Many of the published retrospective studies focus on the benefits of adjuvant RT in terms of survival and recurrence based on stratification by Masaoka stage. More recent studies have focused World Health Organization (WHO) cell type as a factor in establishing a good candidate group for adjuvant RT. In 2009, Utsumi et al.28Utsumi T Shiono H Kadota Y et al.Postoperative radiation therapy after complete resection of thymoma has little impact on survival.Cancer. 2009; 115: 5413-5420Crossref PubMed Scopus (67) Google Scholar published a retrospective study of 324 patients who underwent resection of a thymoma in which 119 were treated with adjuvant RT. When examined based on WHO cell type and Masaoka staging, they showed that patients with stage I and II thymoma as well as WHO types A, AB, and B1 should not receive adjuvant RT. Also, no significant difference in actuarial disease-specific survival rates were found in patients with stage III and IV disease or WHO cell types B2 and B3 who were and were not treated with adjuvant RT.28Utsumi T Shiono H Kadota Y et al.Postoperative radiation therapy after complete resection of thymoma has little impact on survival.Cancer. 2009; 115: 5413-5420Crossref PubMed Scopus (67) Google Scholar Although the dose–response relationship for adjuvant RT is as controversial as the indication(s), RT treatment regimens for thymoma traditionally used doses ranging from 30 to 60 Gy in 1.8 to 2.0 Gy fractions, which were delivered over 3 to 6 weeks.5Nakahara K Ohno K Hashimoto J et al.Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients.J Thorac Cardiovasc Surg. 1988; 95: 1041-1047PubMed Google Scholar, 16Zhu G He S Fu X et al.Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.Int J Radiat Oncol Biol Phys. 2004; 60: 1113-1119Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar, 17Urgesi A Monetti U Rossi G et al.Role of radiation therapy in locally advanced thymoma.Radiother Oncol. 1990; 19: 273-280Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 18Curran Jr, WJ Kornstein MJ Brooks JJ et al.Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.J Clin Oncol. 1988; 6: 1722-1727PubMed Google Scholar, 21Blumberg D Port JL Weksler B et al.Thymoma: a multivariate analysis of factors predicting survival.Ann Thorac Surg. 1995; 60 (discussion 914.): 908-913Abstract Full Text PDF PubMed Scopus (305) Google Scholar, 29Mornex F Resbeut M Richaud P et al.Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer.Int J Radiat Oncol Biol Phys. 1995; 32: 651-659Abstract Full Text PDF PubMed Scopus (94) Google Scholar, 30Ohara K Okumura T Sugahara S et al.The role of preoperative radiotherapy for invasive thymoma.Acta Oncol. 1990; 29: 425-429Crossref PubMed Scopus (27) Google Scholar, 31Myojin M Choi NC Wright CD et al.Stage III thymoma: pattern of failure after surgery and postoperative radiotherapy and its implication for future study.Int J Radiat Oncol Biol Phys. 2000; 46: 927-933Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar, 32Akaogi E Ohara K Mitsui K et al.Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels.J Surg Oncol. 1996; 63: 17-22Crossref PubMed Scopus (46) Google Scholar, 33Arakawa A Yasunaga T Saitoh Y et al.Radiation therapy of invasive thymoma.Int J Radiat Oncol Biol Phys. 1990; 18: 529-534Abstract Full Text PDF PubMed Scopus (34) Google Scholar, 34Urgesi A Monetti U Rossi G et al.Aggressive treatment of intrathoracic recurrences of thymoma.Radiother Oncol. 1992; 24: 221-225Abstract Full Text PDF PubMed Scopus (69) Google Scholar, 35Venuta F Rendina EA Longo F et al.Long-term outcome after multimodality treatment for stage III thymic tumors.Ann Thorac Surg. 2003; 76 (discussion 1872.): 1866-1872Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 36Uematsu 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: 357-360Abstract Full Text PDF PubMed Scopus (69) Google Scholar It was thought that 40 to 45 Gy is sufficient for control of completely resected or microscopic residual disease,37Ogawa K Uno T Toita T et al.Postoperative radiotherapy for patients with completely resected thymoma: a mult-institutional, retrospective review of 103 patients.Cancer. 2002; 94: 1405-1413Crossref PubMed Scopus (119) Google Scholar but in a retrospective study of 175 patients, Zhu et al.16Zhu G He S Fu X et al.Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.Int J Radiat Oncol Biol Phys. 2004; 60: 1113-1119Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar showed that increasing the dose slightly to 50 Gy might be beneficial. Their data suggested that RT dose >50 Gy is a prognostic factor for 5-year survival, but extending the radiation field prophylactically did not yield greater local control.16Zhu G He S Fu X et al.Radiotherapy and prognostic factors for thymoma: a retrospective study of 175 patients.Int J Radiat Oncol Biol Phys. 2004; 60: 1113-1119Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Zhu et al. suggest that at least 50 Gy should be used for unresectable disease, whereas other studies show >60 Gy is likely necessary for incompletely resected or gross disease.19Ciernik IF Meier U Lutolf UM Prognostic factors and outcome of incompletely resected invasive thymoma following radiation therapy.J Clin Oncol. 1994; 12: 1484-1490Crossref PubMed Scopus (87) Google Scholar, 29Mornex F Resbeut M Richaud P et al.Radiotherapy and chemotherapy for invasive thymomas: a multicentric retrospective review of 90 cases. The FNCLCC trialists. Federation Nationale des Centres de Lutte Contre le Cancer.Int J Radiat Oncol Biol Phys. 1995; 32: 651-659Abstract Full Text PDF PubMed Scopus (94) Google Scholar Sugie et al.38Sugie 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: 75-81Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar suggested adjuvant mediastinal RT with 30 to 40 Gy for stage II and 50 to 55 Gy for stage III prevented local recurrence, and low-dose entire hemithorax irradiation with 11.2 Gy in 7 fractions or 15 to 16 Gy in 10 fractions after removal of disseminated lesions in the pleura helped to control pleural metastases. Because thymomas have been shown to be sensitive to chemotherapy39Daugaard G Hansen HH Rorth M Combination chemotherapy for malignant thymoma.Ann Intern Med. 1983; 99: 189-190Crossref PubMed Scopus (37) Google Scholar as well as RT, multimodality treatment with preoperative chemotherapy and surgical resection followed by adjuvant RT has been shown to increase resectability and survival in patients with stage III and IV thymomas when compared with surgery alone.35Venuta F Rendina EA Longo F et al.Long-term outcome after multimodality treatment for stage III thymic tumors.Ann Thorac Surg. 2003; 76 (discussion 1872.): 1866-1872Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 40Kaghad M Bonnet H Yang A et al.Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.Cell. 1997; 90: 809-819Abstract Full Text Full Text PDF PubMed Scopus (1509) Google Scholar, 41Macchiarini P Chella A Ducci F et al.Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma.Cancer. 1991; 68: 706-713Crossref PubMed Scopus (165) Google Scholar Cisplatin, alone or in combination with other agents (e.g., cyclophosphamide, doxorubicin, vincristine, prednisone, or epirubicin), has demonstrated response rates between 77 and 100%, pathologic complete response rates between 4 and 31%, and R0 resections achievable in 57 to 82% of cases. Cohort survival with these multimodality regimens ranged between 57 and 95%, showing that cisplatin-based neoadjuvant chemotherapy, surgery, and adjuvant RT provides excellent results for those with previously unresectable stage III and IV disease.35Venuta F Rendina EA Longo F et al.Long-term outcome after multimodality treatment for stage III thymic tumors.Ann Thorac Surg. 2003; 76 (discussion 1872.): 1866-1872Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 40Kaghad M Bonnet H Yang A et al.Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.Cell. 1997; 90: 809-819Abstract Full Text Full Text PDF PubMed Scopus (1509) Google Scholar, 41Macchiarini P Chella A Ducci F et al.Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma.Cancer. 1991; 68: 706-713Crossref PubMed Scopus (165) Google Scholar A regimen of combination chemotherapy and definitive RT has also provided reasonable results for unresectable thymomas. A prospective, phase II intergroup study reported a prolonged progression-free survival in patients treated with two to fou
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