Editorial
Postoperative Radiotherapy: Not All Thymic Malignancies Are Created Equal Andreas Rimner, MD
INTRODUCTION Thymomas and thymic carcinomas are rare malignancies of the anterior mediastinum. The mainstay of definitive treatment is surgical resection with or without chemotherapy and/or radiation therapy (RT). Because of the rarity of thymic malignancies, systematic studies of outcomes with different treatment approaches have largely been limited to retrospective, single-institution studies spanning a large time frame. Clear reporting guidelines had been lacking until recently when the International Thymic Malignancies Interest Group (ITMIG) published definitions and reporting guidelines for surgical1 and RT management.2 In this issue of Cancer, Omasa et al3 explore the role of postoperative radiotherapy (PORT) in a large, multi-institutional, retrospective database of the Japanese Association for Research on the Thymus. They specifically analyze the role of PORT in 1265 patients with stage II or III thymoma or thymic carcinoma. The authors should be commended on having collected one of the largest data sets on this important question for an orphan disease. PORT FOR THYMOMA To date, studies on the role of PORT for patients with thymoma have resulted in conflicting outcomes and conclusions. For patients with stage II thymomas, most studies have shown minimal or no improvement with PORT. Berman et al4 reported one of the largest single-institution studies in a population of completely resected patients with stage II thymomas and found that the recurrence rates were low both with and without adjuvant RT (0% vs 8%, nonsignificant). Similar results were reported by Rena et al5 and Chen et al.6 For patients with stage III thymoma, some studies found an improvement in progression-free survival, disease-free survival, or overall survival (OS). Curran et al7 reported a 5-year mediastinal relapse rate of 53% without RT, a rate of 0% with PORT, and a rate of 21% with PORT for patients with subtotal resections. Similarly, Ogawa et al8 reported no mediastinal failure after surgical resection and postoperative mediastinal irradiation. Weksler et al9 detected a benefit in disease-free survival with the addition of adjuvant RT in a large population-based analysis of stage III thymoma. Most other population-based studies have reported similar results and have shown no benefit for stage I to IIA thymomas, a marginal questionable benefit for stage IIB thymomas, and a clearer benefit for stage III to IV thymomas with the addition of adjuvant RT.10-12 Omasa et al3 report that PORT was not associated with improved recurrence-free survival (RFS) or OS in patients with thymomas. However, a common problem with any retrospective data set is the referral bias that is inherent to any consideration of additional adjuvant therapy, including PORT, because patients with adverse high-risk tumor characteristics or suboptimal surgical management such as incomplete resections are more likely to be referred for PORT. This is especially likely in a predominantly surgical database in which the decision about the referral for PORT is most likely made by the operating surgeon rather than a multidisciplinary team. In agreement with this assumption, in the current study, patients who received PORT had a higher proportion of subtotal resections with macroscopic residual disease. Despite this imbalance, there was no difference in RFS or OS between the groups, and this may in fact indicate that PORT may have reduced and overcome the risk for recurrence in incompletely resected patients to levels comparable to those of patients with completely resected thymoma. In addition, interestingly, the majority of patients in this data set had stage II
Corresponding author: Andreas Rimner, MD, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065; Fax: (212) 639-2417; [email protected] Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York See referenced original article on pages 1008-16, this issue. DOI: 10.1002/cncr.29164, Received: November 5, 2014; Accepted: November 6, 2014, Published online January 6, 2015 in Wiley Online Library (wileyonlinelibrary.com)
972
Cancer
April 1, 2015
Postoperative RT for Thymic Malignancies/Rimner
disease, which, according to the literature available to date, would have a smaller benefit with PORT. This may have further reduced any potential impact of PORT on RFS or OS in the subset of patients with thymoma. Therefore, the absence of an improvement in RFS or OS in an imbalanced retrospective data set with a significant potential for referral bias should not be interpreted as the absence of a positive effect of PORT but has to be interpreted with caution. Certainly in the absence of level 1 evidence, patients with adverse tumor features, incomplete resections, or close margins should continue to be considered for PORT on the basis of general oncologic principles after a careful weighing of the risks and benefits of PORT. PORT FOR THYMIC CARCINOMA For the thymic carcinoma subset, patients who received PORT had a higher proportion of subtotal resections with macroscopic residual disease. Despite this imbalance, the authors found a clear RFS benefit associated with PORT. PORT was associated with a 5-year RFS rate of 91.3% for stage II thymic carcinoma (68.1% without PORT) and with a 5-year RFS rate of 50.5% for stage III thymic carcinomas (26.1% without PORT). After adjustments for the Masaoka stage and residual tumor after resection, the hazard ratio of PORT was 0.48 and highly significant. This effect even held up when they analyzed only the subset of patients with complete resections (Table 7). In agreement with the findings of Omasa et al,3 there is increasing evidence that RT is of particular benefit to patients with thymic carcinoma. The recently published results of the largest thymic carcinoma database of ITMIG (with >1000 patients) confirm the results of this study.13 Ahmad et al13 detected a significant improvement with the use of RT in both RFS and OS. Adjuvant RT was used in 42% to 67% of the patients across all stages, including patients with earlystage disease and R0 resections. The most significant prognostic factors associated with an improvement in RFS were the use of RT and male sex. An R0 resection status was of borderline significance, and this suggests that PORT is at least in part able to negate the recurrence risk of an incomplete resection. The most significant factors associated with improved OS were the use of RT and an R0 resection status. As mentioned by Omasa et al, another report based on the European Society of Thoracic Surgeons database came to similar conclusions and detected an OS benefit with the use of adjuvant radiotherapy as well.14 Other factors associated with improved OS in the report by the European SociCancer
April 1, 2015
ety of Thoracic Surgeons included earlier stages and complete resection versus subtotal resection. PORT: IMPACT OF FAILURE PATTERNS, BIOLOGY, AND TECHNICAL ASPECTS Thus, the findings of this study support the notion that thymomas and thymic carcinomas are distinct entities, as stated by the new World Health Organization classification.15 The failure patterns also differ between these diseases, and this may play a role in the value of adding PORT. While thymomas predominantly fail in the pleural space,16 thymic carcinomas have a higher risk of distant recurrence.17 The more aggressive biological behavior of thymic carcinomas may extend to the risk of not only distant failure but also local failure, even in the setting of a complete resection, and thus result in the strong beneficial effect of PORT observed. However, as mentioned previously, PORT may still benefit patients with thymoma because patients with PORT did equally as well as those without PORT despite the imbalance of several adverse factors in patients with PORT. Generally, thymic malignancies are considered quite radiosensitive. The biological basis for this is not well explored. Recently, the Cancer Genome Atlas initiative of the National Cancer Institute started the Rare Tumor Characterization Project, in which 124 thymomas submitted by participating ITMIG institutions are included (http://cancergenome.nih.gov/cancersselected/Thymoma). It is hoped that the findings from such a large effort will contribute to our understanding of the underlying tumor biology and radiation responsiveness. Epigenetic and immunologic characteristics may further help to identify patients who would benefit from PORT the most. The true impact of PORT is difficult to interpret in a retrospective data set without technical details on the delivery of PORT. Although it may be difficult to collect such details in a retrospective, nationwide database such as that used in this study by Omasa et al,3 it is highly recommended that the ITMIG treatment and reporting guidelines be followed in future prospective and retrospective studies. Only with detailed information on patient immobilization, radiation field design, dose calculation algorithms, doses to the postoperative bed and normal tissues, radiation delivery techniques, respiratory motion management, and onboard imaging will it be possible to draw meaningful conclusions about the role of PORT. The quality of PORT delivered will undoubtedly affect the rates of tumor control, short- and long-term toxicity, and outcomes. 973
Editorial
FUTURE OUTLOOK Ultimately, prospective studies are needed to determine the role of PORT in thymic malignancies. ITMIG has initiated a multi-institutional database that will prospectively collect many of these RT details as well as details on surgery, chemotherapy, pathology, radiology, and patient outcomes.18 Such a database may provide significantly greater insight into the true impact of PORT. A randomized study of the role of PORT would provide the ultimate level of evidence, but this is a challenging task because of the rarity of the disease, the long follow-up needed, and the low rate of events. Pending such a study, patients will need full disclosure about the potential benefits and risks of PORT to make an informed decision. Overall, the role of PORT for patients with stage II and III thymoma remains controversial. Although PORT likely has an impact on RFS in patients with adverse features or subtotal resection, its role in completely resected patients is unclear, and there remains a lack of level 1 evidence. However, for patients with thymic carcinoma, there is now increasing evidence from at least 3 large retrospective databases that PORT is beneficial. For such a rare disease, this may be the best evidence for the role of PORT that we will be able to obtain. FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES Andreas Rimner reports grants and personal fees from Varian Medical Systems, Boehringer Ingelheim, General Electric, and Bristol Myers-Squibb outside the submitted work.
REFERENCES 1. Detterbeck FC, Moran C, Huang J, et al. Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol. 2011;6(suppl 3): S1730-S1738.
974
2. Gomez D, Komaki R, Yu J, Ikushima H, Bezjak A. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol. 2011;6(suppl 3):S1743-S1748. 3. Omasa M, Date H, Sozu T, et al. Postoperative radiotherapy is effective for thymic carcinoma but not for thymoma in stage II to III thymic epithelial tumors: the Japanese Association for Research on the Thymus Database Study. Cancer. 2015;121:1008-1016. 4. Berman AT, Litzky L, Livolsi V, et al. Adjuvant radiotherapy for completely resected stage 2 thymoma. Cancer. 2011;117:3502-3508. 5. Rena O, Papalia E, Oliaro A, et al. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma? Eur J Cardiothorac Surg. 2007;31:109-113. 6. Chen YD, Feng QF, Lu HZ, et al. Role of adjuvant radiotherapy for stage II thymoma after complete tumor resection. Int J Radiat Oncol Biol Phys. 2010;78:1400-1406. 7. Curran WJ Jr, Kornstein MJ, Brooks JJ, Turrisi AT III. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol. 1988;6:1722-1727. 8. 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. 9. Weksler B, Shende M, Nason KS, Gallagher A, Ferson PF, Pennathur A. The role of adjuvant radiation therapy for resected stage III thymoma: a population-based study. Ann Thorac Surg. 2012;93:1822-1829. 10. 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. 11. Forquer JA, Rong N, Fakiris AJ, Loehrer Sr PJ, Johnstone PAS. Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease. Int J Radiat Oncol Biol Phys. 2010;76:440-445. 12. Patel S, MacDonald OK, Nagda S, Bittner N, Suntharalingam M. Evaluation of the role of radiation therapy in the management of malignant thymoma. Int J Radiat Oncol Biol Phys. 2012;82:17971801. 13. Ahmad U, Yao X, Detterbeck FC, et al. Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg. In press. 14. Ruffini E, Detterbeck F, Van Raemdonck D, et al. Thymic carcinoma: a cohort study of patients from the European Society of Thoracic Surgeons database. J Thorac Oncol. 2014;9:541-548. 15. Travis WD, Brambilla E, Burke A, Marx A, Nicholson A. World Health Organization Classification of Tumours, Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart; Lyon, France: International Agency for Research on Cancer. In press. 16. Rimner A, Gomez DR, Wu AJ, et al. Failure patterns relative to radiation treatment fields for stage II-IV thymoma. J Thorac Oncol. 2014;9:403-409. 17. Huang J, Rizk NP, Travis WD, et al. Comparison of patterns of relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg. 2009;138:26-31. 18. Detterbeck FC. The International Thymic Malignancy Interest Group. J Natl Compr Canc Netw. 2013;11:589-593.
Cancer
April 1, 2015
Copyright of Cancer (0008543X) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Postoperative Radiotherapy: Not All Thymic Malignancies Are Created Equal Andreas Rimner, MD
INTRODUCTION Thymomas and thymic carcinomas are rare malignancies of the anterior mediastinum. The mainstay of definitive treatment is surgical resection with or without chemotherapy and/or radiation therapy (RT). Because of the rarity of thymic malignancies, systematic studies of outcomes with different treatment approaches have largely been limited to retrospective, single-institution studies spanning a large time frame. Clear reporting guidelines had been lacking until recently when the International Thymic Malignancies Interest Group (ITMIG) published definitions and reporting guidelines for surgical1 and RT management.2 In this issue of Cancer, Omasa et al3 explore the role of postoperative radiotherapy (PORT) in a large, multi-institutional, retrospective database of the Japanese Association for Research on the Thymus. They specifically analyze the role of PORT in 1265 patients with stage II or III thymoma or thymic carcinoma. The authors should be commended on having collected one of the largest data sets on this important question for an orphan disease. PORT FOR THYMOMA To date, studies on the role of PORT for patients with thymoma have resulted in conflicting outcomes and conclusions. For patients with stage II thymomas, most studies have shown minimal or no improvement with PORT. Berman et al4 reported one of the largest single-institution studies in a population of completely resected patients with stage II thymomas and found that the recurrence rates were low both with and without adjuvant RT (0% vs 8%, nonsignificant). Similar results were reported by Rena et al5 and Chen et al.6 For patients with stage III thymoma, some studies found an improvement in progression-free survival, disease-free survival, or overall survival (OS). Curran et al7 reported a 5-year mediastinal relapse rate of 53% without RT, a rate of 0% with PORT, and a rate of 21% with PORT for patients with subtotal resections. Similarly, Ogawa et al8 reported no mediastinal failure after surgical resection and postoperative mediastinal irradiation. Weksler et al9 detected a benefit in disease-free survival with the addition of adjuvant RT in a large population-based analysis of stage III thymoma. Most other population-based studies have reported similar results and have shown no benefit for stage I to IIA thymomas, a marginal questionable benefit for stage IIB thymomas, and a clearer benefit for stage III to IV thymomas with the addition of adjuvant RT.10-12 Omasa et al3 report that PORT was not associated with improved recurrence-free survival (RFS) or OS in patients with thymomas. However, a common problem with any retrospective data set is the referral bias that is inherent to any consideration of additional adjuvant therapy, including PORT, because patients with adverse high-risk tumor characteristics or suboptimal surgical management such as incomplete resections are more likely to be referred for PORT. This is especially likely in a predominantly surgical database in which the decision about the referral for PORT is most likely made by the operating surgeon rather than a multidisciplinary team. In agreement with this assumption, in the current study, patients who received PORT had a higher proportion of subtotal resections with macroscopic residual disease. Despite this imbalance, there was no difference in RFS or OS between the groups, and this may in fact indicate that PORT may have reduced and overcome the risk for recurrence in incompletely resected patients to levels comparable to those of patients with completely resected thymoma. In addition, interestingly, the majority of patients in this data set had stage II
Corresponding author: Andreas Rimner, MD, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065; Fax: (212) 639-2417; [email protected] Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York See referenced original article on pages 1008-16, this issue. DOI: 10.1002/cncr.29164, Received: November 5, 2014; Accepted: November 6, 2014, Published online January 6, 2015 in Wiley Online Library (wileyonlinelibrary.com)
972
Cancer
April 1, 2015
Postoperative RT for Thymic Malignancies/Rimner
disease, which, according to the literature available to date, would have a smaller benefit with PORT. This may have further reduced any potential impact of PORT on RFS or OS in the subset of patients with thymoma. Therefore, the absence of an improvement in RFS or OS in an imbalanced retrospective data set with a significant potential for referral bias should not be interpreted as the absence of a positive effect of PORT but has to be interpreted with caution. Certainly in the absence of level 1 evidence, patients with adverse tumor features, incomplete resections, or close margins should continue to be considered for PORT on the basis of general oncologic principles after a careful weighing of the risks and benefits of PORT. PORT FOR THYMIC CARCINOMA For the thymic carcinoma subset, patients who received PORT had a higher proportion of subtotal resections with macroscopic residual disease. Despite this imbalance, the authors found a clear RFS benefit associated with PORT. PORT was associated with a 5-year RFS rate of 91.3% for stage II thymic carcinoma (68.1% without PORT) and with a 5-year RFS rate of 50.5% for stage III thymic carcinomas (26.1% without PORT). After adjustments for the Masaoka stage and residual tumor after resection, the hazard ratio of PORT was 0.48 and highly significant. This effect even held up when they analyzed only the subset of patients with complete resections (Table 7). In agreement with the findings of Omasa et al,3 there is increasing evidence that RT is of particular benefit to patients with thymic carcinoma. The recently published results of the largest thymic carcinoma database of ITMIG (with >1000 patients) confirm the results of this study.13 Ahmad et al13 detected a significant improvement with the use of RT in both RFS and OS. Adjuvant RT was used in 42% to 67% of the patients across all stages, including patients with earlystage disease and R0 resections. The most significant prognostic factors associated with an improvement in RFS were the use of RT and male sex. An R0 resection status was of borderline significance, and this suggests that PORT is at least in part able to negate the recurrence risk of an incomplete resection. The most significant factors associated with improved OS were the use of RT and an R0 resection status. As mentioned by Omasa et al, another report based on the European Society of Thoracic Surgeons database came to similar conclusions and detected an OS benefit with the use of adjuvant radiotherapy as well.14 Other factors associated with improved OS in the report by the European SociCancer
April 1, 2015
ety of Thoracic Surgeons included earlier stages and complete resection versus subtotal resection. PORT: IMPACT OF FAILURE PATTERNS, BIOLOGY, AND TECHNICAL ASPECTS Thus, the findings of this study support the notion that thymomas and thymic carcinomas are distinct entities, as stated by the new World Health Organization classification.15 The failure patterns also differ between these diseases, and this may play a role in the value of adding PORT. While thymomas predominantly fail in the pleural space,16 thymic carcinomas have a higher risk of distant recurrence.17 The more aggressive biological behavior of thymic carcinomas may extend to the risk of not only distant failure but also local failure, even in the setting of a complete resection, and thus result in the strong beneficial effect of PORT observed. However, as mentioned previously, PORT may still benefit patients with thymoma because patients with PORT did equally as well as those without PORT despite the imbalance of several adverse factors in patients with PORT. Generally, thymic malignancies are considered quite radiosensitive. The biological basis for this is not well explored. Recently, the Cancer Genome Atlas initiative of the National Cancer Institute started the Rare Tumor Characterization Project, in which 124 thymomas submitted by participating ITMIG institutions are included (http://cancergenome.nih.gov/cancersselected/Thymoma). It is hoped that the findings from such a large effort will contribute to our understanding of the underlying tumor biology and radiation responsiveness. Epigenetic and immunologic characteristics may further help to identify patients who would benefit from PORT the most. The true impact of PORT is difficult to interpret in a retrospective data set without technical details on the delivery of PORT. Although it may be difficult to collect such details in a retrospective, nationwide database such as that used in this study by Omasa et al,3 it is highly recommended that the ITMIG treatment and reporting guidelines be followed in future prospective and retrospective studies. Only with detailed information on patient immobilization, radiation field design, dose calculation algorithms, doses to the postoperative bed and normal tissues, radiation delivery techniques, respiratory motion management, and onboard imaging will it be possible to draw meaningful conclusions about the role of PORT. The quality of PORT delivered will undoubtedly affect the rates of tumor control, short- and long-term toxicity, and outcomes. 973
Editorial
FUTURE OUTLOOK Ultimately, prospective studies are needed to determine the role of PORT in thymic malignancies. ITMIG has initiated a multi-institutional database that will prospectively collect many of these RT details as well as details on surgery, chemotherapy, pathology, radiology, and patient outcomes.18 Such a database may provide significantly greater insight into the true impact of PORT. A randomized study of the role of PORT would provide the ultimate level of evidence, but this is a challenging task because of the rarity of the disease, the long follow-up needed, and the low rate of events. Pending such a study, patients will need full disclosure about the potential benefits and risks of PORT to make an informed decision. Overall, the role of PORT for patients with stage II and III thymoma remains controversial. Although PORT likely has an impact on RFS in patients with adverse features or subtotal resection, its role in completely resected patients is unclear, and there remains a lack of level 1 evidence. However, for patients with thymic carcinoma, there is now increasing evidence from at least 3 large retrospective databases that PORT is beneficial. For such a rare disease, this may be the best evidence for the role of PORT that we will be able to obtain. FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES Andreas Rimner reports grants and personal fees from Varian Medical Systems, Boehringer Ingelheim, General Electric, and Bristol Myers-Squibb outside the submitted work.
REFERENCES 1. Detterbeck FC, Moran C, Huang J, et al. Which way is up? Policies and procedures for surgeons and pathologists regarding resection specimens of thymic malignancy. J Thorac Oncol. 2011;6(suppl 3): S1730-S1738.
974
2. Gomez D, Komaki R, Yu J, Ikushima H, Bezjak A. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol. 2011;6(suppl 3):S1743-S1748. 3. Omasa M, Date H, Sozu T, et al. Postoperative radiotherapy is effective for thymic carcinoma but not for thymoma in stage II to III thymic epithelial tumors: the Japanese Association for Research on the Thymus Database Study. Cancer. 2015;121:1008-1016. 4. Berman AT, Litzky L, Livolsi V, et al. Adjuvant radiotherapy for completely resected stage 2 thymoma. Cancer. 2011;117:3502-3508. 5. Rena O, Papalia E, Oliaro A, et al. Does adjuvant radiation therapy improve disease-free survival in completely resected Masaoka stage II thymoma? Eur J Cardiothorac Surg. 2007;31:109-113. 6. Chen YD, Feng QF, Lu HZ, et al. Role of adjuvant radiotherapy for stage II thymoma after complete tumor resection. Int J Radiat Oncol Biol Phys. 2010;78:1400-1406. 7. Curran WJ Jr, Kornstein MJ, Brooks JJ, Turrisi AT III. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol. 1988;6:1722-1727. 8. 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. 9. Weksler B, Shende M, Nason KS, Gallagher A, Ferson PF, Pennathur A. The role of adjuvant radiation therapy for resected stage III thymoma: a population-based study. Ann Thorac Surg. 2012;93:1822-1829. 10. 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. 11. Forquer JA, Rong N, Fakiris AJ, Loehrer Sr PJ, Johnstone PAS. Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease. Int J Radiat Oncol Biol Phys. 2010;76:440-445. 12. Patel S, MacDonald OK, Nagda S, Bittner N, Suntharalingam M. Evaluation of the role of radiation therapy in the management of malignant thymoma. Int J Radiat Oncol Biol Phys. 2012;82:17971801. 13. Ahmad U, Yao X, Detterbeck FC, et al. Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg. In press. 14. Ruffini E, Detterbeck F, Van Raemdonck D, et al. Thymic carcinoma: a cohort study of patients from the European Society of Thoracic Surgeons database. J Thorac Oncol. 2014;9:541-548. 15. Travis WD, Brambilla E, Burke A, Marx A, Nicholson A. World Health Organization Classification of Tumours, Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart; Lyon, France: International Agency for Research on Cancer. In press. 16. Rimner A, Gomez DR, Wu AJ, et al. Failure patterns relative to radiation treatment fields for stage II-IV thymoma. J Thorac Oncol. 2014;9:403-409. 17. Huang J, Rizk NP, Travis WD, et al. Comparison of patterns of relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg. 2009;138:26-31. 18. Detterbeck FC. The International Thymic Malignancy Interest Group. J Natl Compr Canc Netw. 2013;11:589-593.
Cancer
April 1, 2015
Copyright of Cancer (0008543X) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
