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Bayram D, Sekmek S, Kayaalp M, Bardakçı M, Hafızoğlu E, Uçar G, Algin E, Bal O, Civelek B, Şendur MAN, Kos FT, Uncu D. Clinical features and prognostic factors in thymoma and thymic carcinoma. Indian J Thorac Cardiovasc Surg 2024; 40:660-668. [PMID: 39416339 PMCID: PMC11473478 DOI: 10.1007/s12055-024-01741-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 04/08/2024] [Accepted: 04/16/2024] [Indexed: 10/19/2024] Open
Abstract
Introduction Thymic epithelial tumors represent the most common cause of anterior mediastinal masses in adults. Among these tumors, thymomas constitute the majority, whereas thymic carcinomas are less prevalent and associated with a poorer prognosis. This study seeks to investigate the clinical and prognostic factors of these rare entities, thymoma, and thymic carcinomas. Materials and methods We conducted a retrospective analysis on a cohort of 60 patients diagnosed with thymoma and thymic carcinoma, who were under follow-up at our clinic between January 1998 and February 2023. The clinical characteristics and prognostic factors of these patients were analyzed separately. Results Thymomas accounted for 75% of the cases. The median age at diagnosis was 46 years in both patient groups. Masaoka stage 4 was observed in 28.9% of thymoma patients and 66.7% of thymic carcinoma patients. The median overall survival (mOS) for thymoma patients was 261.4 months, while it was 9.23 months for patients with thymic carcinoma. Curative surgery emerged as a prognostic factor significantly influencing overall survival in both thymoma and thymic carcinoma patients. Conclusion Our study highlights the significance of Eastern Cooperative Oncology Group (ECOG) performance status and curative surgery as prognostic factors affecting overall survival in thymoma patients. In thymic carcinoma, only curative surgery was found as a prognostic factor. These findings may enhance patient care and guide personalized treatment strategies. Further investigations and prospective studies are warranted to corroborate and expand upon these results.
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Affiliation(s)
- Doğan Bayram
- Department of Medical Oncology, Ankara City Hospital, Ankara, 06000 Turkey
| | - Serhat Sekmek
- Department of Medical Oncology, Ankara City Hospital, Ankara, 06000 Turkey
| | - Mehmet Kayaalp
- Department of Medical Oncology, Ankara University, Ankara, Turkey
| | - Murat Bardakçı
- Department of Medical Oncology, Ankara City Hospital, Ankara, 06000 Turkey
| | - Emre Hafızoğlu
- Department of Medical Oncology, Ankara City Hospital, Ankara, 06000 Turkey
| | - Gökhan Uçar
- Department of Medical Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Efnan Algin
- Department of Medical Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Oznur Bal
- Department of Medical Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Burak Civelek
- Department of Medical Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Mehmet Ali Nahit Şendur
- Department of Medical Oncology, Ankara City Hospital, University of Yildirim Beyazit, Ankara, Turkey
| | - Fahriye Tugba Kos
- Department of Medical Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
| | - Dogan Uncu
- Department of Medical Oncology, Ankara City Hospital, University of Health Sciences, Ankara, Turkey
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2
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Dumont J, Bou-Gharios J, Keller A, Chambrelant I, Pamart G, Mascaux C, Falcoz PE, Antoni D, Olland A, Pietta GA, Noël G. Impact of adjuvant radiotherapy and chemotherapy on thymoma. Cancer Radiother 2024; 28:174-181. [PMID: 38182482 DOI: 10.1016/j.canrad.2023.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/01/2023] [Accepted: 08/03/2023] [Indexed: 01/07/2024]
Abstract
PURPOSE Thymoma is a rare tumour. The most common treatment for thymoma is surgical resection, while the use of radiotherapy and chemotherapy remains controversial. PATIENTS AND METHODS We conducted a monocentric observational study of 31 patients diagnosed with thymoma from June 2004 to July 2020 at cancer centre in Strasbourg, France. We analysed the outcomes of the patients. RESULTS The 2- and 5- year locoregional relapse-free survival rates were 96.3% (95% confidence interval [CI]: 76.5-99.5%) and 68.0% (95% CI: 43.8-83.5%), respectively. Radiotherapy and chemotherapy significantly improved local tumour control (P=0.0008 and 0.04, respectively), while a larger initial tumour size significantly worsened local control rates (P=0.04). The 5- and 10-year overall survival rates were 87.1% (95% CI: 69.2-95%) and 81.7% (95% CI: 60.3-92.2%), respectively. The median overall survival was not reached, and no favourable factor was retrieved. For relapsed patients, the median overall survival after relapse was 115 months. CONCLUSION Despite the inherent limitations of retrospective studies with a limited patient sample size, we demonstrated that chemotherapy and radiotherapy in addition to surgery were effective in achieving local control and contributed to improving patient outcomes in thymoma. Notably, an aggressive treatment strategy at the time of relapse resulted in favourable outcomes for retreated patients.
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Affiliation(s)
- J Dumont
- Chest Diseases Department, Hôpital Hautepierre, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67000 Strasbourg, France
| | - J Bou-Gharios
- Radiation Therapy Department, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, 67200 Strasbourg, France
| | - A Keller
- Radiation Therapy Department, Oncopole, Toulouse, France
| | - I Chambrelant
- Radiation Therapy Department, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, 67200 Strasbourg, France
| | - G Pamart
- Chest Diseases Department, Hôpital Hautepierre, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67000 Strasbourg, France
| | - C Mascaux
- Chest Diseases Department, Hôpital Hautepierre, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67000 Strasbourg, France
| | - P-E Falcoz
- Department of Thoracic Surgery, Hôpital Hautepierre, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67200 Strasbourg, France
| | - D Antoni
- Radiation Therapy Department, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, 67200 Strasbourg, France
| | - A Olland
- Department of Thoracic Surgery, Hôpital Hautepierre, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67200 Strasbourg, France
| | - G A Pietta
- Radiation Therapy Department, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, 67200 Strasbourg, France
| | - G Noël
- Radiation Therapy Department, Institut de cancérologie Strasbourg Europe (ICANS), 17, rue Albert-Calmette, 67200 Strasbourg, France.
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Köksoy EB, Akbulut H. A late relapse thymoma and pure red cell aplasia case with an over 5 years of clinical response under everolimus. Anticancer Drugs 2023; 34:1193-1195. [PMID: 37823284 DOI: 10.1097/cad.0000000000001504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
Although several agents showed some clinical activity in patients with recurrent thymoma, there is no standard treatment option. Here, we report a late relapse thymoma and pure red cell aplasia case, responsive to everolimus with over 5 years of clinical benefit following multiple lines of treatment. Everolimus controlled the rapidly progressive disease in our patient without significant toxicity.
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Affiliation(s)
- Elif B Köksoy
- Department of Medical Oncology, Ankara University, School of Medicine, Ankara, Turkey
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4
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Alqaidy D. Thymoma: An Overview. Diagnostics (Basel) 2023; 13:2982. [PMID: 37761349 PMCID: PMC10527963 DOI: 10.3390/diagnostics13182982] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/15/2023] [Accepted: 09/16/2023] [Indexed: 09/29/2023] Open
Abstract
Thymomas are considered one of the most prevalent types of mediastinal epithelial tumors, which frequently develop in the anterior mediastinum. Due to their rarity, these tumors' nomenclature, classification, and staging are likely to be the subject of debate and argument for most expert pathologists. Furthermore, the significance of thymoma histologic classifications have been debated over the past twenty years. While certain advocates argue that staging at the time of diagnosis is more significant, others believe that histologic subtyping has a significant impact on how patients behave clinically. In this review, we will focus on some of the challenges that diagnostic surgical pathologists may experience while evaluating the histopathology of thymomas and staging these tumors. We will additionally glance over the clinical characteristics of these distinct tumors and the current management strategy.
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Affiliation(s)
- Doaa Alqaidy
- Department of Pathology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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5
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Xu C, Zhang Y, Wang W, Wang Q, Li Z, Song Z, Wang J, Yu J, Liu J, Zhang S, Cai X, Wu M, Zhan P, Liu H, Lv T, Miao L, Min L, Li J, Liu B, Yuan J, Jiang Z, Lin G, Chen X, Pu X, Rao C, Lv D, Yu Z, Li X, Tang C, Zhou C, Zhang J, Guo H, Chu Q, Meng R, Liu X, Wu J, Hu X, Fang M, Zhou J, Zhu Z, Chen X, Pan W, Pang F, Zhou Y, Jian Q, Wang K, Wang L, Zhu Y, Yang G, Lin X, Cai J, Liang L, Feng H, Wang L, Du Y, Yao W, Shi X, Niu X, Yuan D, Yao Y, Huang J, Zhang Y, Sun P, Wang H, Ye M, Wang D, Wang Z, Hao Y, Wang Z, Wan B, Lv D, Yu G, Li A, Kang J, Zhang J, Zhang C, Chen H, Shi L, Ye L, Wang G, Wang Y, Gao F, Zhou W, Hu C, Wei J, Li B, Li Z, Li Y, Liu Z, Yang N, Wu L, Wang Q, Huang W, Hong Z, Wang G, Fang M, Fang Y, Zhu X, Du K, Ji J, et alXu C, Zhang Y, Wang W, Wang Q, Li Z, Song Z, Wang J, Yu J, Liu J, Zhang S, Cai X, Wu M, Zhan P, Liu H, Lv T, Miao L, Min L, Li J, Liu B, Yuan J, Jiang Z, Lin G, Chen X, Pu X, Rao C, Lv D, Yu Z, Li X, Tang C, Zhou C, Zhang J, Guo H, Chu Q, Meng R, Liu X, Wu J, Hu X, Fang M, Zhou J, Zhu Z, Chen X, Pan W, Pang F, Zhou Y, Jian Q, Wang K, Wang L, Zhu Y, Yang G, Lin X, Cai J, Liang L, Feng H, Wang L, Du Y, Yao W, Shi X, Niu X, Yuan D, Yao Y, Huang J, Zhang Y, Sun P, Wang H, Ye M, Wang D, Wang Z, Hao Y, Wang Z, Wan B, Lv D, Yu G, Li A, Kang J, Zhang J, Zhang C, Chen H, Shi L, Ye L, Wang G, Wang Y, Gao F, Zhou W, Hu C, Wei J, Li B, Li Z, Li Y, Liu Z, Yang N, Wu L, Wang Q, Huang W, Hong Z, Wang G, Fang M, Fang Y, Zhu X, Du K, Ji J, Shen Y, Zhang Y, Ma S, Song Y, Lu Y, Liu A, Fang W, Zhong W. Chinese expert consensus on the diagnosis and treatment of thymic epithelial tumors. Thorac Cancer 2023; 14:1102-1117. [PMID: 36924056 PMCID: PMC10125784 DOI: 10.1111/1759-7714.14847] [Show More Authors] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 02/23/2023] [Indexed: 03/18/2023] Open
Abstract
Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first- and second-line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow-up of TETs.
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Affiliation(s)
- Chunwei Xu
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, People's Republic of China.,Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, People's Republic of China.,Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Yongchang Zhang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Wenxian Wang
- Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, People's Republic of China
| | - Qian Wang
- Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People's Republic of China
| | - Ziming Li
- Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Zhengbo Song
- Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, People's Republic of China
| | - Jiandong Wang
- Department of Pathology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Jinpu Yu
- Department of Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Jingjing Liu
- Department of Thoracic Cancer, Jilin Cancer Hospital, Jilin, People's Republic of China
| | - Shirong Zhang
- Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Xiuyu Cai
- Department of VIP Inpatient, Sun Yet-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Ming Wu
- Department of Thoracic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, People's Republic of China
| | - Ping Zhan
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Hongbing Liu
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Tangfeng Lv
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Liyun Miao
- Department of Respiratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Lingfeng Min
- Department of Respiratory Medicine, Clinical Medical School of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, People's Republic of China
| | - Jiancheng Li
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, People's Republic of China
| | - Baogang Liu
- Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China
| | - Jingping Yuan
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Zhansheng Jiang
- Derpartment of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Gen Lin
- Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, People's Republic of China
| | - Xiaohui Chen
- Department of Thoracic Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, People's Republic of China
| | - Xingxiang Pu
- Department of Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Chuangzhou Rao
- Department of Radiotherapy and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, People's Republic of China
| | - Dongqing Lv
- Department of Pulmonary Medicine, Taizhou Hospital of Wenzhou Medical University, Taizhou, People's Republic of China
| | - Zongyang Yu
- Department of Respiratory Medicine, the 900th Hospital of the Joint Logistics Team (the Former Fuzhou General Hospital), Fujian Medical University, Fuzhou, People's Republic of China
| | - Xiaoyan Li
- Department of Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Chuanhao Tang
- Department of Medical Oncology, Peking University International Hospital, Beijing, People's Republic of China
| | - Chengzhi Zhou
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University(The First Affiliated Hospital of Guangzhou Medical University), Guangzhou, People's Republic of China
| | - Junping Zhang
- Department of Thoracic Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan, People's Republic of China
| | - Hui Guo
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Qian Chu
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Rui Meng
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xuewen Liu
- Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Jingxun Wu
- Department of Medical Oncology, the First Affiliated Hospital of Medicine, Xiamen University, Xiamen, People's Republic of China
| | - Xiao Hu
- Zhejiang Key Laboratory of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Zhejiang, People's Republic of China
| | - Min Fang
- Zhejiang Key Laboratory of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Zhejiang, People's Republic of China
| | - Jin Zhou
- Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology, Chengdu, People's Republic of China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Xiaofeng Chen
- Department of Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People's Republic of China
| | - Weiwei Pan
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, People's Republic of China
| | - Fei Pang
- Department of Medical, Shanghai OrigiMed Co, Ltd, Shanghai, People's Republic of China
| | - Yuxiang Zhou
- Department of Medical, Shanghai OrigiMed Co, Ltd, Shanghai, People's Republic of China
| | - Qijie Jian
- Department of Medical, Shanghai OrigiMed Co, Ltd, Shanghai, People's Republic of China
| | - Kai Wang
- Department of Medical, Shanghai OrigiMed Co, Ltd, Shanghai, People's Republic of China
| | - Liping Wang
- Department of Oncology, Baotou Cancer Hospital, Baotou, People's Republic of China
| | - Youcai Zhu
- Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, The Third Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China
| | - Guocai Yang
- Department of Thoracic Surgery, Zhoushan Hospital, Wenzhou Medical University, Zhejiang, People's Republic of China
| | - Xinqing Lin
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University(The First Affiliated Hospital of Guangzhou Medical University), Guangzhou, People's Republic of China
| | - Jing Cai
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Lijun Liang
- Department of Thoracic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, People's Republic of China
| | - Huijing Feng
- Department of Thoracic Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan, People's Republic of China
| | - Lin Wang
- Department of Pathology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan, People's Republic of China
| | - Yingying Du
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Wang Yao
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xuefei Shi
- Department of Respiratory Medicine, Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, People's Republic of China
| | - Xiaomin Niu
- Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Dongmei Yuan
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Yanwen Yao
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Jianhui Huang
- Department of Oncology, Lishui Municipal Central Hospital, Lishui, People's Republic of China
| | - Yinbin Zhang
- Department of Oncology, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Pingli Sun
- Department of Pathology, The Second Hospital of Jilin University, Changchun, People's Republic of China
| | - Hong Wang
- Senior Department of Oncology, The 5th Medical Center of PLA General Hospital, Beijing, People's Republic of China
| | - Mingxiang Ye
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Dong Wang
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Zhaofeng Wang
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Yue Hao
- Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, People's Republic of China
| | - Zhen Wang
- Department of Radiation Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Bing Wan
- Department of Respiratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Donglai Lv
- Department of Clinical Oncology, The 901 Hospital of Joint Logistics Support Force of People Liberation Army, Hefei, People's Republic of China
| | - Genhua Yu
- Department of Radiation Oncology, Zhebei Mingzhou Hospital, Huzhou, People's Republic of China
| | - Anna Li
- Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou, People's Republic of China
| | - Jin Kang
- Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou, People's Republic of China
| | - Jiatao Zhang
- Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou, People's Republic of China
| | - Chao Zhang
- Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou, People's Republic of China
| | - Huafei Chen
- Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, The Third Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China
| | - Lin Shi
- Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Leiguang Ye
- Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China
| | - Gaoming Wang
- Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yina Wang
- Department of Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Feng Gao
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
| | - Wei Zhou
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, People's Republic of China
| | - Chunxiu Hu
- Department of Cancer Radiotherapy and Chemotherapy, Zhejiang Queue Hospital, Quzhou, People's Republic of China
| | - Jianguo Wei
- Department of Pahtology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, People's Republic of China
| | - Bihui Li
- Department of Oncology, The Second Affiliated Hospital of Guilin Medical University, Guilin, People's Republic of China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yuan Li
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Zhefeng Liu
- Senior Department of Oncology, The 5th Medical Center of PLA General Hospital, Beijing, People's Republic of China
| | - Nong Yang
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Lin Wu
- Department of Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Qiming Wang
- Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University Henan Cancer Hospital, Zhengzhou, People's Republic of China
| | - Wenbin Huang
- Department of Pathology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People's Republic of China
| | - Zhuan Hong
- Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, People's Republic of China
| | - Guansong Wang
- Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Meiyu Fang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Yong Fang
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, People's Republic of China
| | - Xixu Zhu
- Department of Radiation Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Kaiqi Du
- Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, The Third Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China
| | - Jiansong Ji
- Department of Radiology, Lishui Municipal Central Hospital, Lishui, People's Republic of China
| | - Yi Shen
- Department of Thoracic Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Yiping Zhang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Shenglin Ma
- Department of Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou Cancer Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Yong Song
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Yuanzhi Lu
- Department of Clinical Pathology, The First Affiliated Hospital Of Jinan University, Guangzhou, People's Republic of China
| | - Anwen Liu
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Wenfeng Fang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Wenzhao Zhong
- Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou, People's Republic of China
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6
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Takeuchi S, Hirata K. Pet imaging in thymomas. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00208-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Sphingomonas and Phenylobacterium as Major Microbiota in Thymic Epithelial Tumors. J Pers Med 2021; 11:jpm11111092. [PMID: 34834444 PMCID: PMC8623653 DOI: 10.3390/jpm11111092] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/18/2021] [Accepted: 10/23/2021] [Indexed: 12/14/2022] Open
Abstract
The microbiota has been reported to be closely associated with carcinogenesis and cancer progression. However, its involvement in the pathology of thymoma remains unknown. In this study, we aimed to identify thymoma-specific microbiota using resected thymoma samples. Nineteen thymoma tissue samples were analyzed through polymerase chain reaction amplification and 16S rRNA gene sequencing. The subjects were grouped according to histology, driver mutation status in the GTF2I gene, PD-L1 status, and smoking habits. To identify the taxa composition of each sample, the operational taxonomic units (OTUs) were classified on the effective tags with 97% identity. The Shannon Index of the 97% identity OTUs was calculated to evaluate the alpha diversity. The linear discriminant analysis effect size (LEfSe) method was used to compare the relative abundances of all the bacterial taxa. We identified 107 OTUs in the tumor tissues, which were classified into 26 genera. Sphingomonas and Phenylobacterium were identified as abundant genera in almost all the samples. No significant difference was determined in the alpha diversity within these groups; however, type A thymoma tended to exhibit a higher bacterial diversity than type B thymoma. Through the LEfSe analysis, we identified the following differentially abundant taxa: Bacilli, Firmicutes, and Lactobacillales in type A thymoma; Proteobacteria in type B thymoma; Gammaproteobacteria in tumors harboring the GTF2I mutation; and Alphaproteobacteria in tumors without the GTF2I mutation. In conclusion, Sphingomonas and Phenylobacterium were identified as dominant genera in thymic epithelial tumors. These genera appear to comprise the thymoma-specific microbiota.
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Süveg K, Putora PM, Joerger M, Iseli T, Fischer GF, Ammann K, Glatzer M. Radiotherapy for thymic epithelial tumours: a review. Transl Lung Cancer Res 2021; 10:2088-2100. [PMID: 34012817 PMCID: PMC8107733 DOI: 10.21037/tlcr-20-458] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Thymic epithelial tumours (TETs) represent a rare disease, yet they are the most common tumours of the anterior mediastinum. Due to the rare occurrence of TETs, evidence on optimal treatment is limited. Surgery is the treatment of choice in the management of TETs, while the role of postoperative radiotherapy (PORT) remains unresolved. PORT remains debated for thymomas, especially in completely resected stage II tumours, for which PORT may be more likely to benefit in the presence of aggressive histology (WHO subtype B2, B3) or extensive transcapsular invasion (Masaoka-Koga stage IIB). For stage III thymoma, evidence suggests an overall survival (OS) benefit for PORT after complete resection. For incompletely resected thymomas stage II or higher PORT is recommended. Thymic carcinomas at any stage with positive resection margins should be offered PORT. Radiotherapy plays an important role in the management of unresectable locally advanced TETs. Induction therapy (chemotherapy or chemoradiation) followed by surgery may be useful for locally advanced thymic malignancies initially considered as unresectable. Chemotherapy only is offered in patients with unresectable, metastatic tumours in palliative intent, checkpoint inhibitors may be promising for refractory diseases. Due to the lack of high-level evidence and the importance of a multidisciplinary approach, TETs should be discussed within a multidisciplinary team and the final recommendation should reflect individual patient preferences.
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Affiliation(s)
- Krisztian Süveg
- Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Paul Martin Putora
- Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.,Department of Radiation Oncology, University of Bern, Bern, Switzerland
| | - Markus Joerger
- Department of Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Thomas Iseli
- Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Galina Farina Fischer
- Departmet of Radiology and Nuclear Medicine, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Karlheinz Ammann
- Department of Thoracic Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Markus Glatzer
- Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland
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Kamata S, Ishida I, Suzuki Y, Oura H. Single-center evaluation of prognostic factors for thymoma treated by surgery: a retrospective study. J Cardiothorac Surg 2021; 16:8. [PMID: 33413522 PMCID: PMC7791864 DOI: 10.1186/s13019-020-01386-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 12/10/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study aimed to retrospectively evaluate the clinical, pathological, and treatment-related factors associated with survival in patients with surgically treated thymomas. METHODS Sixty patients with thymomas who underwent treatment at our institution between 2004 and 2015 were included. Survival analysis was performed based on curves that were obtained using the Kaplan-Meier method. The Wilcoxon test was used for all comparisons, and p < 0.05 was considered statistically significant. RESULTS Forty-seven, four, three, four, and two patients presented tumor stages I, II, III, IVa, and IVb (according to the Masaoka classification), respectively, while six, 14, 11, 22, and seven patients had type A, AB, B1, B2, and B3 thymomas, respectively. Furthermore, 53 and eight patients underwent complete resection and required additional resection of adjacent organs, respectively, and no patients died from surgery-related complications. The five-year survival and recurrence-free survival (RFS) rates were 96 and 86%, respectively. The five-year survival rate for all stages was 100% except for those with stage IVb tumors (Masaoka classification); the survival rate for those patients was 0%. Separately, the five-year RFS rates for tumor stages I, II, III, IVa, and IVb were 100, 91, 91, 81, and 71%, respectively. Finally, the five-year survival rates in cases with complete and incomplete resections were 100 and 71%, respectively, indicating that the latter group had a significantly poorer prognosis (p < 0.001). CONCLUSIONS These findings suggest that complete resection and the Masaoka pathological stage are significant predictors of prognosis in patients with thymomas. Surgery should aim to achieve complete resection; however, advanced cases may require multimodality therapy.
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Affiliation(s)
- Satoshi Kamata
- Iwate Prefectural Central Hospital, Department of Thoracic Surgery, Ueda 1-4-1, Morioka, 020-0066, Japan.
| | - Itaru Ishida
- Iwate Prefectural Central Hospital, Department of Thoracic Surgery, Ueda 1-4-1, Morioka, 020-0066, Japan
| | - Yuyo Suzuki
- Iwate Prefectural Central Hospital, Department of Thoracic Surgery, Ueda 1-4-1, Morioka, 020-0066, Japan
| | - Hiroyuki Oura
- Iwate Prefectural Central Hospital, Department of Thoracic Surgery, Ueda 1-4-1, Morioka, 020-0066, Japan
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Yokoyama S, Miyoshi H. Comparison of PD-L1 immunohistochemical assays and the significance of PD-L1 expression in thymoma. J Thorac Dis 2020; 12:7553-7560. [PMID: 33447446 PMCID: PMC7797863 DOI: 10.21037/jtd-19-3703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Thymoma is a relatively rare malignancy, which is categorized as thymic epithelial tumor but known as the most common pathology that is developed in the anterior mediastinum. Complete resection is recommended for localized tumors and usually favorable prognosis can be obtained. However, poor survival period has been reported in unresectable cases exhibiting extensive invasion or distant metastasis, as effective chemotherapeutic regimens are restrained. We previously assessed expression of programmed death ligand 1 (PD-L1) and programmed death 1 (PD-1) and discussed their prospective application in the immunotherapy of thymic epithelial tumors. After our publication, additional studies using reliable PD-L1 antibodies, which are currently administered to predict efficacy of PD-1/PD-L1 blockade therapy were performed and further characterized PD-L1 in thymoma. Herein, recent knowledge in relation to the significance of PD-L1 expression in thymoma is reviewed based on recent findings using qualified PD-L1 clones. Most studies coherently found high expression of PD-L1 on the cell membrane and cytoplasm of tumor epithelial cells in accordance with previous reports, which is a predictive marker for effectiveness of anti-PD-1/PD-L1 drugs, even when approved PD-L1 antibodies were employed. On the other hand, PD-L1 expression on tumor infiltrating immune cells remains to be sufficiently determined. High PD-L1 expression can be expected in cases with high grade histological subtypes, such as type B2/B3 thymomas, or those with advanced stages III or IV of the disease. Interestingly, the level of PD-L1 expression was found to be upregulated after chemotherapy compared with that before, which could be explained by immunogenic cell death. The prognostic impact of PD-L1 expression in thymoma might be found only when thymic carcinoma patients were excluded. Furthermore, it also could be identified when we analyzed thymomas completely resected, distinct from biopsy and incompletely resected cases.
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Affiliation(s)
- Shintaro Yokoyama
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
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11
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Primary Driver Mutations in GTF2I Specific to the Development of Thymomas. Cancers (Basel) 2020; 12:cancers12082032. [PMID: 32722121 PMCID: PMC7466068 DOI: 10.3390/cancers12082032] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/16/2020] [Accepted: 07/22/2020] [Indexed: 12/17/2022] Open
Abstract
Thymomas are rare mediastinal tumors that are difficult to treat and pose a major public health concern. Identifying mutations in target genes is vital for the development of novel therapeutic strategies. Type A thymomas possess a missense mutation in GTF2I (chromosome 7 c.74146970T>A) with high frequency. However, the molecular pathways underlying the tumorigenesis of other thymomas remain to be elucidated. We aimed to detect this missense mutation in GTF2I in other thymoma subtypes (types B). This study involved 22 patients who underwent surgery for thymomas between January 2014 and August 2019. We isolated tumor cells from formalin-fixed paraffin-embedded tissues from the primary lesions using laser-capture microdissection. Subsequently, we performed targeted sequencing to detect mutant GTF2I coupled with molecular barcoding. We used PyClone analysis to determine the fraction of tumor cells harboring mutant GTF2I. We detected the missense mutation (chromosome 7 c.74146970T>A) in GTF2I in 14 thymomas among the 22 samples (64%). This mutation was harbored in many type B thymomas as well as type A and AB thymomas. The allele fraction for the tumors containing the mutations was variable, primarily owing to the coexistence of normal lymphocytes in the tumors, especially in type B thymomas. PyClone analysis revealed a high cellular prevalence of mutant GTF2I in tumor cells. Mutant GTF2I was not detected in other carcinomas (lung, gastric, colorectal, or hepatocellular carcinoma) or lymphomas. In conclusion, the majority of thymomas harbor mutations in GTF2I that can be potentially used as a novel therapeutic target in patients with thymomas.
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Markowiak T, Koller M, Zeman F, Huppertz G, Hofmann HS, Ried M. Protocol of a retrospective, multicentre observational study on hyperthermic intrathoracic chemotherapy in Germany. BMJ Open 2020; 10:e041511. [PMID: 32690754 PMCID: PMC7375498 DOI: 10.1136/bmjopen-2020-041511] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Objective of the 'German hyperthermic intrathoracic chemotherapy (HITOC) study' is to evaluate the HITOC as additional treatment after surgical cytoreduction for malignant pleural tumours. Even though HITOC is applied with increasing frequency, there is no standardised therapy protocol concerning the technique of HITOC, the selection as well as dosage of chemotherapeutic agents and perioperative management in order to provide a safe and comparable, standardised treatment regime. METHODS AND ANALYSIS This trial is a retrospective, multicentre observational study, which is funded by the German Research Foundation. Approximately 300 patients will be included. Four departments of thoracic surgery, which are performing the most HITOC procedures in Germany, are contributing to this study: Center for Thoracic Surgery at the University Hospital Regensburg, Thoracic Clinic Heidelberg of the University of Heidelberg, Center for Thoracic Surgery of the Hospital University of Munich and the Department of Thoracic Surgery at the University Hospital Freiburg. All patients who underwent surgical cytoreduction and subsequent HITOC at one of the four centres between starting the HITOC programme in 2008 and December 2019 will be included. Information on the performed HITOC will be obtained, focusing on the technique as well as the applied perfusion solution including the chemotherapeutic agent. Furthermore, parameters of the patient's postoperative recovery will be analysed to determine 30-day morbidity and mortality. ETHICS AND DISSEMINATION The approvals by the local ethics committee of the respective clinic and the three participating clinics have been obtained. The results will be presented in conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER German Clinical Trials Registry (DRKS00015012; Pre-results).
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Affiliation(s)
- Till Markowiak
- Department of Thoracic Surgery, Universitätsklinikum Regensburg, Regensburg, Bayern, Germany
| | - Michael Koller
- Center for Clinical Studies, Universitätsklinikum Regensburg, Regensburg, Bayern, Germany
| | - Florian Zeman
- Center for Clinical Studies, Universitätsklinikum Regensburg, Regensburg, Bayern, Germany
| | - Gunnar Huppertz
- Center for Clinical Studies, Universitätsklinikum Regensburg, Regensburg, Bayern, Germany
| | - Hans-Stefan Hofmann
- Department of Thoracic Surgery, Universitätsklinikum Regensburg, Regensburg, Bayern, Germany
| | - Michael Ried
- Department of Thoracic Surgery, Universitätsklinikum Regensburg, Regensburg, Bayern, Germany
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Abstract
Resection is the mainstay of treatment for thymic epithelial tumors (TETs), with complete removal of the tumor and involved organs being the ultimate aim. The choice of surgical approach plays a major role in defining treatment success, and the optimal choice of method should thus provide an adequate surgical view to achieve complete tumor resection. While median sternotomy is considered the gold standard for access to the mediastinum, several minimally invasive approaches to thymectomy have been described, including video-assisted robotic-assisted thymectomy, although the oncological outcomes of that procedure remain unclear. A multimodal approach incorporating chemotherapy or chemoradiotherapy followed by extended surgery may improve resectability and outcomes for patients with advanced TETs. Surgical debulking is also reportedly acceptable for invasive thymoma because of its potential for achieving favorable outcomes. Re-resection is an acceptable option for patients with recurrent thymoma after initial resection, and repeat resection for recurrent pleural dissemination seems effective. Here, the literature on current clinical practices in the surgical management and treatment of TETs is reviewed.
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Yu L, Zhang B, Du X, Yu Z, Yang X, Jiang Y. Evaluating the effectiveness of chemotherapy for thymic epithelial tumors using the CD-DST method. Thorac Cancer 2020; 11:1160-1169. [PMID: 32196982 PMCID: PMC7180557 DOI: 10.1111/1759-7714.13362] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 02/01/2020] [Accepted: 02/02/2020] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Thymic epithelial tumors (TET) are frequently eligible for curative-intent surgical resection. For locally advanced TETs, chemotherapy has been used to both reduce the tumor burden and achieve prolonged disease control. However, effective therapy for this disease largely remains to be determined. Here, we report the chemosensitivity of 100 patients with TETs determined by the collagen gel droplet embedded culture-drug sensitivity test (CD-DST). METHODS A total of 100 patients with TETs underwent surgical resection. The efficacy of antitumor agents on TET cells was tested by CD-DST. RESULTS Thymic epithelial tumors were pathologically confirmed after surgery: two cases were type A thymoma, 17 were type AB, 12 were type B1, 44 were type B2, 12 were type B3, and there were 13 cases with thymic carcinoma. A total of 36% patients with TETs were sensitive to different types of chemotherapeutic agents. There was no significant differences in age, histological type, clinical staging, or association with autoimmune diseases between sensitive and nonsensitive cases. Type B1 and B2 thymoma were relatively more sensitive to chemotherapeutic agents (6/12 and 18/44, respectively), while sensitivity of type B3 cases to chemotherapeutic agents was much lower (only 2/12). Cases with type A thymoma were not sensitive to any antitumor drugs. Among 11 chemotherapeutic agents tested in our study, the sensitivity of TETs to EPI was the highest (16%). No patients with thymoma were sensitive to Alimta (Pemetrexed). CONCLUSIONS Our work illuminates the effectiveness of chemotherapy for TETs and provides important clues for choosing antitumor drugs with relatively high drug sensitivity to TETs in advance.
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Affiliation(s)
- Lei Yu
- Department of Thoracic Surgery, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
| | - Bao‐xun Zhang
- Department of Thoracic Surgery, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
| | - Xin Du
- Department of Thoracic Surgery, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
| | - Zhen Yu
- Department of Thoracic Surgery, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
| | - Xing‐guo Yang
- Department of Thoracic Surgery, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
| | - Yu‐xuan Jiang
- Department of Thoracic Surgery, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
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Bian D, Zhao L, Zhang X, Lv F, Zhu Z, Qiu H, Zhang H. Immunohistochemistry biomarker TP53 expression predicts the survival of thymomas. Gland Surg 2020; 9:291-299. [PMID: 32420253 PMCID: PMC7225485 DOI: 10.21037/gs.2020.03.01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 02/08/2020] [Indexed: 11/06/2022]
Abstract
BACKGROUND Thymomas are rare malignancies. Thymectomy is the optimal therapy which could prolong the survival of patients. However, prognostic factors of thymomas are not clear. METHODS Thymomas patients were enrolled from 2001 to 2016. Clinical and pathological prognostic factors of thymomas were evaluated by univariate and multivariate analyses. RESULTS A total number of 98 patients was eligible for this study. All patients were received complete resection (CR). Diagnostic age [elder than the median 60 vs. younger than 60, hazard ratio (HR) =2.325, P=0.027], Masaoka stage (III vs. I, HR =10.756, P<0.001; IV vs. I, HR =6.558, P=0.014), and diabetes mellitus (DM) (with vs. without, HR =0.142, P=0.004) were independent prognostic factors for overall survival (OS). Immunohistochemistry (IHC) biomarker TP53 expression also influenced OS significantly (positive vs. negative, HR =5.157, P=0.018). Furthermore, age (elder than 60 vs. younger than 60, HR =2.980, P=0.022) was independent prognostic factors for recurrence free survival (RFS). CONCLUSIONS We found that diagnostic age, clinical stages, DM, TP53 expression in IHC, and quality perioperative nursing are prognostic factors in thymomas.
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Affiliation(s)
- Dongliang Bian
- Department of Thoracic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China
| | - Liting Zhao
- Department of Thoracic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China
| | - Xuelin Zhang
- Department of Thoracic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China
| | - Fanzhen Lv
- Department of Thoracic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China
| | - Zhenghong Zhu
- Department of Thoracic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China
| | - Hui Qiu
- Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Huibiao Zhang
- Department of Thoracic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai 200040, China
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Conforti F, Pala L, Giaccone G, De Pas T. Thymic epithelial tumors: From biology to treatment. Cancer Treat Rev 2020; 86:102014. [PMID: 32272379 DOI: 10.1016/j.ctrv.2020.102014] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 02/29/2020] [Accepted: 03/19/2020] [Indexed: 11/30/2022]
Abstract
In the last few years, meaningful advances have been made in the knowledge of the biology of Thymic Epithelial Tumors (TETs). Data available suggest that in most cases, the different histological subtypes could be distinct biological entities, characterized by specific molecular aberrations, rather than representing a histological continuum of diseases. Recurrent gene mutations in Thymomas and Thymic Carcinoma have been identified, but we still do not know the exact role played by these mutations in TETs pathogenesis. Relevant new data are now available on the pathogenetic mechanisms underlying the association between TETs and autoimmune diseases that warrant further investigations for the potential therapeutic implications. The progress in knowledge of the molecular pathways involved in TETs pathogenesis, allowed to identify and to test target therapies potentially active in such diseases. Platinum-based chemotherapy remains the standard first line treatment for patients with advanced or metastatic TETs. However, some promising data have been reported on the activity of new target therapies, including anti-angiogenic drugs, Cycline Dependent Kinases and PI3K/mTOR inhibitors, as well as of Immune-checkpoint inhibitors. A number of new drugs and combinations are currently under evaluation. The efficacy of new drugs should be balanced with their toxicity profiles, in such complex patients that seem to be more susceptible to develop drug-related toxicities, in particular with immunotherapies.
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Affiliation(s)
- Fabio Conforti
- Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy.
| | - Laura Pala
- Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | | | - Tommaso De Pas
- Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy
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Kanemura H, Tamura T, Nishimura N, Kobayashi D, Higashi T. Thymic epithelial tumor treatment in Japan: analysis of hospital cancer registry and insurance claims data, 2012-2014. Jpn J Clin Oncol 2020; 50:310-317. [PMID: 31829410 PMCID: PMC7061247 DOI: 10.1093/jjco/hyz167] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 09/04/2019] [Accepted: 10/08/2019] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Thymic epithelial tumors are a rare type of neoplasm. Accordingly, it is difficult to perform phase III trials in patients with thymic epithelial tumors, and thus, no standard treatment has been established for these tumors. In this study, we aimed to investigate the current status of thymic epithelial tumor treatment in Japan. METHODS This retrospective observational study enrolled patients with thymic epithelial tumor whose data were recorded in a nationwide Hospital-based Cancer Registry that was linked with health insurance claims data for the registered patients between 2012 and 2014. The patients' treatment details were obtained from a health insurance claims database. RESULTS A total of 813 patients with thymoma and 547 with thymic carcinoma were included in the analysis. Overall, 549 (67.5%) thymoma patients underwent surgical resection alone. Among patients with thymic carcinoma, 230 (42.0%) underwent initial surgery, and 124 (53.9%) received subsequent radiotherapy and chemotherapy. Chemotherapy regimens varied across the hospitals; overall, 21 and 22 regimens were used to treat thymoma and thymic carcinoma, respectively. Platinum-based combination regimens were predominantly selected for both diseases. CONCLUSIONS This study revealed the real-world patterns of thymic epithelial tumor treatment in Japan. Although the nature of this study did not enable the determination of optimal treatment strategies, the simultaneous analysis of nationwide registry, insurance, efficacy and prognostic data may contribute to the establishment of a standard treatment strategy for rarely occurring cancers such as thymic epithelial tumor.
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Affiliation(s)
- Hiroaki Kanemura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke’s International Hospital, Tokyo, Japan
| | - Tomohide Tamura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke’s International Hospital, Tokyo, Japan
| | - Naoki Nishimura
- Department of Pulmonary Medicine, Thoracic Center, St. Luke’s International Hospital, Tokyo, Japan
| | - Daiki Kobayashi
- Department of Epidemiology, St. Luke’s International University Graduate School of Public Health, Tokyo, Japan
| | - Takahiro Higashi
- Division of Health Services Research, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
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Kang CH. The change of therapeutic trends in the thymic epithelial tumor. J Thorac Dis 2020; 11:5652-5654. [PMID: 32030291 DOI: 10.21037/jtd.2019.11.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Chang Hyun Kang
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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PD-L1 Expression and Tumor-Infiltrating Lymphocytes in Thymic Epithelial Neoplasms. J Clin Med 2019; 8:jcm8111833. [PMID: 31683962 PMCID: PMC6912585 DOI: 10.3390/jcm8111833] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 10/29/2019] [Accepted: 10/30/2019] [Indexed: 12/14/2022] Open
Abstract
Thymic epithelial tumors (TETs) are rare malignant mediastinal tumors that are difficult to diagnose and treat. The programmed death 1 (PD-1) receptor and its ligand (PD-L1) are expressed in various malignant tumors and have emerged as potential immunotherapeutic targets. However, the immunobiology of TETs is poorly understood. We evaluated PD-L1 expression and the presence of tumor-infiltrating lymphocytes (CD8 and CD3 expression) in surgical TET specimens from 39 patients via immunohistochemistry and determined their relation to clinicopathological parameters. Cases with membranous reactivity of the PD-L1 antibody in ≥1% of tumor cells were considered positive. Positive PD-L1 expression was observed in 53.9% of cases. Histologically, PD-L1 expression was positive in 2/6 type A, 2/6 type AB, 3/9 type B1, 4/4 type B2, 5/6 type B3, and 5/8 type C TET cases. Thus, the number of cases with PD-L1 expression and the percent expression of PD-L1 were significantly higher in more aggressive thymomas (type B2 or B3). CD3+ and CD8+ tumor-infiltrating lymphocytes were diffusely and abundantly distributed in all cases. These data suggest that a PD-1/PD-L1 blockade is a promising treatment for TETs, with more beneficial treatment effects for aggressive thymomas such as type B2 or B3.
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Imbimbo M, Ottaviano M, Vitali M, Fabbri A, Leuzzi G, Fiore M, Franceschini D, Pasello G, Perrino M, Schiavon M, Pruneri G, Dei Tos AP, Sangalli C, Garassino MC, Berardi R, Alessi A, Calareso G, Petrini I, Scorsetti M, Scotti V, Rosso L, Rea F, Pastorino U, Casali PG, Ramella S, Ricardi U, Abate-Daga L, Torri V, Trama A, Palmieri G, Marino M, Zucali PA. Best practices for the management of thymic epithelial tumors: A position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME). Cancer Treat Rev 2018; 71:76-87. [PMID: 30366202 DOI: 10.1016/j.ctrv.2018.10.001] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 09/18/2018] [Accepted: 10/03/2018] [Indexed: 12/11/2022]
Abstract
Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series. Often the lack of evidence leads to formulation of indications based on expert opinions. As for other rare cancers it is crucial to create networks to coordinate the work among centres involved in treatment of these diseases in order to offer the best diagnostic and therapeutic tools. For this purpose, in 2014 a network named TYME (ThYmic MalignanciEs), was founded in Italy with the aim of improving care and research in TETs. In September 2017 a panel of multidisciplinary experts from TYME network and from other Italian centres strongly involved in TET diagnosis and treatment convened a first Italian Expert meeting together with representatives of association for patients affected by rare thoracic cancers Tu.To.R, to explore how these tumors are managed in the different centres of Italy compared to ESMO guidelines. In this paper we summarize the issues discussed during that meeting and we propose recommandations based on Masaoka Koga and the new TNM staging system.
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Affiliation(s)
- Martina Imbimbo
- Unit of Thoracic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Margaret Ottaviano
- Rare Tumors Reference Center, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy
| | - Milena Vitali
- Unit of Thoracic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandra Fabbri
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Leuzzi
- Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico di Roma, Italy
| | - Davide Franceschini
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Hospital, Rozzano (Milan), Italy
| | - Giulia Pasello
- Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | - Matteo Perrino
- Department of Medical Oncology, Humanitas Clinical and Research Hospital, Rozzano (Milan), Italy
| | - Marco Schiavon
- Thoracic Surgery Unit Department of Cardio-Thoracic and Vascular Sciences, University of Padova, Italy
| | - Giancarlo Pruneri
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | - Claudia Sangalli
- Department of Radiology and Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | - Rossana Berardi
- Clinica Oncologica, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy
| | - Alessandra Alessi
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giuseppina Calareso
- Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Iacopo Petrini
- General Pathology, Department of Translational Research and New Technologies in Medicine, University of Pisa, Italy
| | - Marta Scorsetti
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Hospital, Rozzano (Milan), Italy; Humanitas University, Department of Biomedical Sciences, Rozzano (Milan), Italy
| | - Vieri Scotti
- Department of Oncology, Radiation Oncology Unit, Careggi University Hospital, Florence, Italy
| | - Lorenzo Rosso
- Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Federico Rea
- Thoracic Surgery Unit Department of Cardio-Thoracic and Vascular Sciences, University of Padova, Italy
| | - Ugo Pastorino
- Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Paolo Giovanni Casali
- Adult Mesenchymal Tumor Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Sara Ramella
- Radiation Oncology, Campus Bio-Medico di Roma, Italy
| | | | | | - Valter Torri
- Laboratory of Methodology for Biomedical Research, IRCCS-Mario Negri Institute for Pharmacological Research, Milan, Italy
| | - Annalisa Trama
- Evaluative Epidemiology Unit-Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovannella Palmieri
- Rare Tumors Reference Center, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy
| | - Mirella Marino
- Department of Pathology, Regina Elena National Cancer Institute, Roma, Italy
| | - Paolo Andrea Zucali
- Department of Medical Oncology, Humanitas Clinical and Research Hospital, Rozzano (Milan), Italy
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Abstract
Thymoma and thymic carcinoma, known as the most common features of thymic epithelial tumors (TETs), are thoracic malignancies displaying varied clinical features and prognosis. These neoplasms being frequently ineligible for surgical complete resection as a curative treatment because of extensive tumor spread, effectual nonsurgical treatments are needed; however, an optimal chemotherapeutic regimen has not been identified, although some regimens have been shown to be active. Immunotherapy is effective for other malignancies and may be promising as a therapeutic alternative for refractory TETs. Thus far, several studies have determined the expression of programmed death ligand 1 (PD-L1) and programmed death 1 (PD-1) in TETs, including its clinicopathological and prognostic significance. The results have been conflicting due to the different immunohistochemical antibodies employed and distinct cutoff values. However, many authors identified abundant PD-L1 expression in TETs, which is considered as an important predictive factor for therapeutic effect of PD-1 inhibitors in other malignant tumors. In some clinical trials, an acceptable clinical efficacy of PD-1 inhibitor for TETs has been reported as expected; however, concerns regarding immunological adverse events have been raised. To optimize these therapeutic agents for refractory TETs, additional studies which evaluate clinical availabilities of immunotherapeutic drugs and characterize their basic mechanisms of action against immunotherapeutic targets are both urgently required.
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Affiliation(s)
- Shintaro Yokoyama
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
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Chaudhuri T, Lakshmaiah KC, Babu G, Dasappa L, Jacob L, Babu MCS, Rudresha AH, Lokesh KN, Rajeev LK. Metastatic thymic epithelial tumors: A regional cancer center experience. Indian J Cancer 2018; 55:288-291. [DOI: 10.4103/ijc.ijc_524_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Banna GL, Sheel A, Sheel V, Bille A, Routledge T, Fernando S, Nair A, Lal R. Treatment and prognostic factors of patients with thymic epithelial tumors at first recurrence or progression. Future Oncol 2017; 13:2429-2439. [PMID: 29121777 PMCID: PMC5967362 DOI: 10.2217/fon-2017-0236] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Accepted: 07/20/2017] [Indexed: 12/26/2022] Open
Abstract
AIM The treatment of patients with recurrent or progressive thymic epithelial tumors remains uncertain due to limited data in this rare disease. MATERIALS & METHODS A retrospective 10-year monoinstitutional analysis was conducted on 25 patients with first recurrence or disease progression following primary treatment. RESULTS Twenty patients had thymoma, five thymic carcinomas. Ten patients (40%) received surgery, four (40%) following chemotherapy; 17 (68%) had chemotherapy, with a combination regimen in 16 of them (94%). Surgery had a significant effect both on overall survival and progression-free survival-2 by univariate analysis (p = 0.04), combination chemotherapy only on progression-free survival-2 (p = 0.03). CONCLUSION Combination chemotherapy and surgery at first recurrence/progression of thymic epithelial tumors were associated with improved survival. DISCUSSION Although several limitations may have affected this retrospective study on a relatively small number of patients with this rare entity of recurrent thymic malignancies, we suggest the use of combination chemotherapy and surgery at their first recurrence may have contributed to the high overall and progression-free survival observed with adequate follow-up and deserve further investigations in broader retrospective and comparative studies.
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Affiliation(s)
- Giuseppe L Banna
- Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK
- Cannizzaro Hospital, via Messina 829, 95126, Catania, Italy
| | - Ankur Sheel
- University of Massachusetts School of Medicine, 55 N Lake Ave, Worcester, MA 01655, USA
| | - Varun Sheel
- University of Massachusetts Amherst, Amherst, MA 01003, USA
| | - Andrea Bille
- Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK
| | - Tom Routledge
- Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK
| | | | - Arjun Nair
- University of Massachusetts Amherst, Amherst, MA 01003, USA
| | - Rohit Lal
- Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK
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Isshiki Y, Tanaka H, Suzuki Y, Yoshida Y. Cyclosporine is a potential curative treatment option for advanced thymoma. Exp Hematol Oncol 2017; 6:13. [PMID: 28473943 PMCID: PMC5415741 DOI: 10.1186/s40164-017-0073-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 04/28/2017] [Indexed: 12/14/2022] Open
Abstract
Background Thymectomy can effectively cure most thymoma patients; however, patients with advanced thymoma typically require chemotherapy, which is associated with limited efficacy in this context. Here we provide the first report of a patient with recurrent thymoma who achieved complete remission (CR) using cyclosporine therapy. Case presentation A 63-year-old woman who had undergone resection surgery for recurrent type B1 thymoma developed pure red cell aplasia (PRCA), and CT findings revealed thymoma recurrence. After the initiation of orally-administered cyclosporine, PRCA quickly resolved, and the thymoma disappeared without the administration of any anti-thymoma therapy. The patient has remained in CR for over 3 years using only cyclosporine. Conclusions This is the first report describing the curative potential of cyclosporine for the treatment of advanced thymoma. Although the mechanism underlying this effect remains unclear, cyclosporine can become a less toxic and more cost-effective treatment option for thymoma compared with conventional therapy. Clinical trials are needed to confirm the therapeutic potential of cyclosporine as a new treatment option for thymoma.
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Affiliation(s)
- Yusuke Isshiki
- Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677 Japan
| | - Hiroaki Tanaka
- Department of Hematology, Asahi General Hospital, Chiba, Japan
| | - Yoshio Suzuki
- Department of Clinical Pathology, Asahi General Hospital, Chiba, Japan
| | - Yukihiro Yoshida
- Department of Respiratory Surgery, Asahi General Hospital, Chiba, Japan
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Luo T, Zhao H, Zhou X. The clinical features, diagnosis and management of recurrent thymoma. J Cardiothorac Surg 2016; 11:140. [PMID: 27580949 PMCID: PMC5007840 DOI: 10.1186/s13019-016-0533-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 08/23/2016] [Indexed: 11/17/2022] Open
Abstract
Thymoma is a disease with malignant potential, which has a recurrence rate after complete resection ranging from 5 to 50 %. Multiple studies on the risk factors, treatment or prognosis have been reported. Many of them are controversial, however. In this review, we summarized some accepted risk factors, means of diagnosis and different treatments of recurrent thymoma. The risk factors of recurrent thymoma haven’t been well-studied, and its management remains controversial. We reviewed the literatures and found some key points which should be noticed during the surgery of initial thymoma. Although reoperation should be taken into account preferentially, multimodal treatments are also available. The prognosis are also been discussed.
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Affiliation(s)
- Taobo Luo
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.,Wenzhou Medical University, Wenzhou, 325035, People's Republic of China
| | - Hongguang Zhao
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China. .,Wenzhou Medical University, Wenzhou, 325035, People's Republic of China. .,Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.
| | - Xinming Zhou
- Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China. .,Wenzhou Medical University, Wenzhou, 325035, People's Republic of China.
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Qian X, Song Z. Efficacy of pemetrexed-based regimen in relapsed advanced thymic epithelial tumors and its association with thymidylate synthetase level. Onco Targets Ther 2016; 9:4527-31. [PMID: 27524908 PMCID: PMC4966498 DOI: 10.2147/ott.s105949] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Purpose Due to the rarity of thymic epithelial tumors (TET), no standard chemotherapy regimen has been identified in the relapsed setting. The aim of this study was to investigate the activity of a pemetrexed-based regimen in advanced TET as palliative treatment after failure of previous chemotherapy, and to detect its association with thymidylate synthetase (TS) level. Methods Patients with pathologically confirmed TET and treated with pemetrexed-based regimen were evaluated from 2006 to 2014 in Zhejiang Cancer Hospital. TS mRNA level was detected by real-time polymerase chain reaction. The Kaplan–Meier method was used for survival analysis. Results A total of 22 TET patients were identified, of whom eight had thymoma and 14 had thymic carcinoma. In total, the objective response rate and disease control rate of the 22 patients were 22.7% and 68.2%, respectively. Median progression-free survival and overall survival were 4.5 months and 34.9 months, respectively. A trend of lower TS mRNA levels existed in patients with disease control compared to those with progressive disease (268.0±160.5×10−4 vs 567.0±445.0×10−4, P=0.065). Conclusion Patients with advanced TET may benefit from pemetrexed-based regimen therapy. TS mRNA level is valuable for predicting the efficacy of pemetrexed in TET.
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Affiliation(s)
- Xinyu Qian
- Department of Chemotherapy, Hangzhou First People's Hospital, Hangzhou Cancer Hospital, Hangzhou
| | - Zhengbo Song
- Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Province; Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China
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27
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Yokoyama S, Miyoshi H, Nakashima K, Shimono J, Hashiguchi T, Mitsuoka M, Takamori S, Akagi Y, Ohshima K. Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma. Clin Cancer Res 2016; 22:4727-34. [PMID: 27166394 DOI: 10.1158/1078-0432.ccr-16-0434] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 05/03/2016] [Indexed: 01/22/2023]
Abstract
PURPOSE The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis. EXPERIMENTAL DESIGN PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR. RESULTS Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1(+) TILs as significant predictors of poor survival, together with Masaoka-Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs. CONCLUSIONS Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727-34. ©2016 AACR.
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Affiliation(s)
- Shintaro Yokoyama
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
| | - Kazutaka Nakashima
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Joji Shimono
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Toshihiro Hashiguchi
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan. Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Masahiro Mitsuoka
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Shinzo Takamori
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Yoshito Akagi
- Department of Surgery, Kurume University School of Medicine, Kurume, Japan
| | - Koichi Ohshima
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
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Weissferdt A, Moran CA. Neuroendocrine Differentiation in Thymic Carcinomas: A Diagnostic Pitfall: An Immunohistochemical Analysis of 27 Cases. Am J Clin Pathol 2016; 145:393-400. [PMID: 27124922 DOI: 10.1093/ajcp/aqv095] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES Neuroendocrine differentiation in carcinomas of the nonneuroendocrine type has been observed in various organ systems. Awareness of this phenomenon is important since such tumors need to be separated from true neuroendocrine neoplasms because of therapeutic and prognostic consequences. To investigate this occurrence in thymic carcinomas, 27 cases of different histologies were analyzed using neuroendocrine immunohistochemical markers. METHODS Twenty-seven conventional thymic carcinomas from thymectomies were studied immunohistochemically with antibodies directed against synaptophysin, chromogranin A, and CD56 in addition to the standard markers for these tumors. RESULTS Focal expression of at least one neuroendocrine marker was identified in a total of 12 (44%) cases. Chromogranin A was positive in five (19%) cases, synaptophysin in eight (30%), and CD56 in 10 (37%). All three markers were coexpressed in four (15%) cases. CONCLUSIONS Neuroendocrine differentiation in conventional thymic carcinomas is a common occurrence. It is imperative to separate these tumors from true neuroendocrine neoplasms of the thymus-especially large cell neuroendocrine carcinoma-since both entities require different treatment modalities and likely show different biologic behavior. Contrary to prior suggestions, neuroendocrine differentiation should not be used to distinguish thymic carcinomas from thymomas, and these tumors should not be regarded as "mixed carcinomas."
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Affiliation(s)
- Annikka Weissferdt
- From the Department of Pathology, MD Anderson Cancer Center, Houston, TX.
| | - Cesar A Moran
- From the Department of Pathology, MD Anderson Cancer Center, Houston, TX
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29
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Fu H, Gu ZT, Fang WT, Fu JH, Shen Y, Han YT, Yu ZT, Li Y, Tan LJ, Pang LW, Chen KN. Long-Term Survival After Surgical Treatment of Thymic Carcinoma: A Retrospective Analysis from the Chinese Alliance for Research of Thymoma Database. Ann Surg Oncol 2016; 23:619-625. [DOI: 10.1245/s10434-015-4825-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Grosch H, Hoffmann H, Weis CA, Thomas M. [Thymus cancers: A clinical observation]. DER PATHOLOGE 2016; 37:91-105; quiz 106. [PMID: 26821326 DOI: 10.1007/s00292-016-0140-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors are rare tumors with an incidence of 0.13/100,000. MATERIALS AND METHODS A literature search was performed to identify recent findings on epidemiology, classification, and various therapeutic approaches. RESULTS These tumors with a wide spectrum of histologic and biologic features may be clinically unapparent for a long time or show a very aggressive behavior with local invasion and distant metastases. Surgical resection is the mainstay in stage I and II thymomas, whereas in stage III thymomas and in thymomas with pleural dissemination surgery in context of a multimodal treatment should be discussed. Thymic tumors are chemoreactive. Targeted therapies show poor results and should only be considered in the palliative situation after failure of chemotherapy. CONCLUSION The new TNM (T: tumor, N: node, M: metastasis) classification of thymic tumors will help to identify the best treatment options.
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Affiliation(s)
- H Grosch
- Abteilung Onkologie, Thoraxklinik Heidelberg, Amalienstraße 5, 69126, Heidelberg, Deutschland.
| | - H Hoffmann
- Abteilung Chirurgie, Thoraxklinik Heidelberg, Heidelberg, Deutschland
| | - C-A Weis
- Abteilung Pathologie, Universitätsklinikum Mannheim, Mannheim, Deutschland
| | - M Thomas
- Abteilung Onkologie, Thoraxklinik Heidelberg, Amalienstraße 5, 69126, Heidelberg, Deutschland
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Clinicopathologic and Prognostic Implications of Programmed Death Ligand 1 Expression in Thymoma. Ann Thorac Surg 2016; 101:1361-9. [PMID: 26794891 DOI: 10.1016/j.athoracsur.2015.10.044] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 09/12/2015] [Accepted: 10/13/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Programmed death ligand 1 (PD-L1) has been reported to be expressed in various malignancies and is considered to be a prognostic factor and an immunotherapeutic target. The aim of this study was to characterize PD-L1 expression in thymoma and determine statistical associations between this expression and clinical features. METHODS We reviewed formalin-fixed, paraffin-embedded tissue specimens from 82 thymoma cases accumulated at Kurume University, the majority of which achieved surgical complete resection. Expression of PD-L1 was evaluated by immunohistochemistry. Statistical associations between PD-L1 expression and clinicopathologic features were evaluated by using χ(2) test and Fisher's exact test. Disease-free survival and overall survival curves were established by the Kaplan-Meier method and compared using a log-rank test. Predictive factors for disease-free survival after complete resection were analyzed by using a Cox proportional hazards model in univariate and multivariate analysis. RESULTS Overall, 44 thymoma cases (54%) revealed high PD-L1 expression. High PD-L1 expression was statistically associated with Masaoka stage III/IV disease (p = 0.043) and World Health Organization type B2 or B3 thymoma (p = 0.044). Disease-free survival after complete resection in high PD-L1 expression was significantly worse than that in low PD-L1 expression (p = 0.021), although there was no significant difference in overall survival (p = 0.957). Multivariate analysis also revealed high PD-L1 expression as an independent risk factor for recurrence (p = 0.008). CONCLUSIONS Characterization of PD-L1 expression in thymoma should enable more effective clinical approaches, including prognostic stratification of patients and potential use of anti-PD-L1 antibody immunotherapy.
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A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors. J Thorac Oncol 2015; 10:1800-6. [DOI: 10.1097/jto.0000000000000692] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Song Z, Yu X, Zhang Y. Chemotherapy and prognosis in advanced thymic carcinoma patients. Clinics (Sao Paulo) 2015; 70:775-80. [PMID: 26735216 PMCID: PMC4676312 DOI: 10.6061/clinics/2015(12)03] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 08/26/2015] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the prognostic factors for patients with advanced thymic carcinoma. METHODS A retrospective review of the medical records of 86 patients treated with chemotherapy for advanced thymic carcinoma was conducted between 2000 and 2012 at our institution. The clinical characteristics, chemotherapy regimens and prognostic factors were analyzed. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazard model was used for multivariate analysis. RESULTS Of the 86 patients, 56 were male and 30 were female. The median survival time was 24.5 months. For the first-line chemotherapy treatment, the objective response rate was 47.7% and the disease control rate was 80.2%. The median progression-free survival for all patients was 6.5 months for first-line chemotherapy. No significant differences in progression-free survival were observed among the different chemotherapy regimens. Multivariate analyses revealed that the prognostic factors for overall survival included performance status (p=0.043), histology grade (p=0.048), and liver metastasis (p=0.047). CONCLUSION Our results suggest that there is no difference in efficacy between multiagent and doublet regimens. The prognosis of patients with advanced thymic carcinoma can be predicted based on histological grade, liver metastasis and performance status.
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Affiliation(s)
- Zhengbo Song
- Zhejiang Cancer Hospital, Department of Medical Oncology, Hangzhou, China
| | - Xinmin Yu
- Zhejiang Cancer Hospital, Department of Medical Oncology, Hangzhou, China
| | - Yiping Zhang
- Zhejiang Cancer Hospital, Department of Medical Oncology, Hangzhou, China
- Corresponding author: E-mail:
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34
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Phase II Study of Amrubicin Combined with Carboplatin for Thymic Carcinoma and Invasive Thymoma: North Japan Lung Cancer Group Study 0803. J Thorac Oncol 2014; 9:1805-9. [DOI: 10.1097/jto.0000000000000362] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Response to cytotoxic chemotherapy in patients previously treated with palliative-intent chemotherapy for advanced thymic carcinoma. Clin Lung Cancer 2014; 16:221-7. [PMID: 25468802 DOI: 10.1016/j.cllc.2014.10.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/23/2014] [Accepted: 10/28/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND Clinical efficacy of second- and later-line chemotherapy for patients with thymic carcinoma previously treated with chemotherapy remains uncertain; limited data are available about this carcinoma because of its rarity. The aim of this study was to investigate effective chemotherapy for patients with thymic carcinoma previously treated with chemotherapy using a retrospective analysis of responses and times to event. PATIENTS AND METHODS We conducted a retrospective review of the medical records of 23 advanced thymic carcinoma patients previously treated with palliative-intent chemotherapy between 1980 and 2014 in our institution. Clinical demographic characteristics, agents, response, and time to treatment failure for each treatment line and overall survival were reviewed. Factors expected to be associated with survival rates were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. RESULTS The study included 13 men (56.5%) and 10 women (43.5%). The median age at diagnosis was 58.5 years. The most common histological subtypes were squamous cell carcinoma (16 patients [69.6%]), followed by neuroendocrine carcinoma (4 patients [17.4%]). The objective response rates of first-, second-, third-, and fourth-line chemotherapy were 60.9%, 39.1%, 23.1%, and 25.0%, respectively. The median survival time was 18.8 months (95% confidence interval, 7.5-40.9 months). Uni- and multivariate analyses of all assessed variables failed to identify any statistically significant indicators of overall survival. CONCLUSION Patients with thymic carcinoma previously treated with palliative-intent chemotherapy might respond to second- or later-lines of cytotoxic chemotherapy.
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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 2014; 141:323-31. [PMID: 25146529 PMCID: PMC4293490 DOI: 10.1007/s00432-014-1800-6] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Accepted: 08/07/2014] [Indexed: 11/26/2022]
Abstract
Purpose
Thymic malignancies, comprising thymoma and thymic carcinoma, are rare. Consequently, optimal chemotherapy for advanced thymic malignancies remains controversial. Platinum-based chemotherapy is currently the consensus treatment based on the results of single-arm phase II trials and retrospective investigations. However, comparison of cisplatin-based and carboplatin-based chemotherapy has yet to be undertaken; the effectiveness of the addition of anthracycline also remains uncertain. Methods In the present study, clinical trials and retrospective data regarding platinum-based chemotherapy were analyzed. The endpoint was the response rate to each chemotherapy. For advanced thymoma, we compared platinum with anthracycline-based chemotherapy and platinum with non-anthracycline-based chemotherapy. For advanced thymic carcinoma, anthracycline-based versus non-anthracycline-based chemotherapy and carboplatin-based versus cisplatin-based chemotherapy were compared. This analysis included a retrospective study of response of advanced thymic carcinoma to irinotecan and cisplatin in our institution. Results The response rate for the 314 patients from 15 studies with advanced thymoma, including both prospective and retrospective data, was 69.4 % [95 % confidence interval (CI) 63.1–75.0 %] for platinum with anthracycline-based chemotherapy and 37.8 % (95 % CI 28.1–48.6 %; p < 0.0001) for platinum with non-anthracycline-based chemotherapy. The response rates after anthracycline-based and non-anthracycline-based chemotherapy for advanced thymic carcinoma were similar (41.8 vs. 40.9 %; p < 0.91), whereas the response rates after cisplatin-based and carboplatin-based chemotherapy for advanced thymic carcinoma differed significantly (53.6 vs. 32.8 %; p = 0.0029) in 206 patients from 10 studies. Conclusions Platinum with anthracycline-based chemotherapy is an optimal combination for advanced thymoma. For advanced thymic carcinoma, cisplatin-based chemotherapy may be superior to carboplatin-based chemotherapy.
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The potency of curative-intent treatment for advanced thymic carcinoma. Lung Cancer 2014; 84:175-81. [DOI: 10.1016/j.lungcan.2014.02.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2013] [Revised: 01/24/2014] [Accepted: 02/19/2014] [Indexed: 11/23/2022]
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Clinical outcomes with chemotherapy for advanced thymic carcinoma. Lung Cancer 2013; 80:75-80. [DOI: 10.1016/j.lungcan.2012.12.012] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2012] [Revised: 12/02/2012] [Accepted: 12/05/2012] [Indexed: 12/31/2022]
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Abstract
AIM Thymomas are rare in children. Our aim was to review clinical and pathologic characteristics and outcome in children with thymomas. PATIENTS AND METHODS Between 1979 and 2011, 11 children with thymomas were diagnosed. Hospital files were reviewed for presenting complaints, clinical, radiologic, and other laboratory data, surgical practices, chemotherapy and radiotherapy outcomes. RESULTS Median age was 8 years (range, 1 to 13 y). Male to female ratio was 9/2. Most common initial complaints were dyspnea, cough, chest pain, and fever. Median time from onset of symptoms was 1 month (range, 0.23 to 3 mo). Associated conditions including hyper-IgE syndrome, hypogammaglobulinemia, and systemic lupus erythematosus plus idiopathic thrombocytopenic purpura were present in 3 patients. Chest x-rays and/or thoracic computed tomographies displayed thymic hyperplasia and/or masses in anterior mediastinum accompanied by pleural (n = 2) and pericardial effusions (n = 1), pulmonary metastases (n = 1), and cervical lymph node metastasis (n = 1). Compression or invasion of trachea or vessels was documented in 5 cases. Seven cases underwent initial tumor resection; others experienced open or trucut biopsies. Histopathologically, 5 cases had invasive and 6 had benign thymomas. Benign thymomas did not receive any postoperative treatment; all cases are disease free at a median follow-up of 211 months. Three of 5 cases with invasive thymomas underwent surgery, 4/5 received chemotherapy and external radiotherapy (3600 to 4500 cGy). Two invasive thymomas died of disease. Three cases with invasive thymomas are disease free at a median follow-up of 209 months. CONCLUSIONS Benign thymomas have excellent prognosis. For invasive thymomas with or without metastasis, radiotherapy, and chemotherapy offers survival advantage. Complete surgical resection may increase chances for cure.
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Neuhaus T, Luyken J. Long lasting efficacy of sorafenib in a heavily pretreated patient with thymic carcinoma. Target Oncol 2012; 7:247-51. [PMID: 23090205 DOI: 10.1007/s11523-012-0235-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Accepted: 10/08/2012] [Indexed: 12/23/2022]
Abstract
Thymoma and thymic carcinoma are rare neoplasms of the mediastinum, arising from the epithelial cells of the thymus. While surgical resection is the treatment of choice in early stages, platin-based chemotherapy is mainly used in patients with advanced or metastatic disease; however, the prognosis is poor. Here we present the case of a 54 year old female patient suffering from a CD117-negative thymic carcinoma with widespread metastases. After several courses of different kinds of chemotherapy, finally these approaches failed to be effective. Thus we initiated a treatment with sorafenib, an inhibitor of several receptor tyrosine kinases. The treatment was tolerated very well, and within a few weeks the general condition of the patient improved significantly. A CT-scan, performed 3 months after therapy with sorafenib started, showed a 50 % reduction of tumor size, and this effect lasted for 15 months. When the carcinoma relapsed again, we administered another course of chemotherapy and, because of lacking success, we even tried to use sunitinib. However, the patient died in a septic shock, based on progressive disease. In summary, we present a patient with metastastic thymic carcinoma, in which sorafenib led to a tumor-control for 18 months.
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41
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Evans TL. Emerging treatment options for patients with recurrent advanced thymic epithelial tumors. Onco Targets Ther 2012; 5:177-84. [PMID: 22973113 PMCID: PMC3439855 DOI: 10.2147/ott.s23267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The purpose of this review article is to review recent advances in the treatment of advanced thymic epithelial tumors. These tumors are generally responsive to cytotoxic combination chemotherapy in the first-line setting. While newer agents have shown efficacy in the salvage setting, there is no one standard approach. A multitude of targeted agents have shown promise generally in case reports, though as of yet, nothing has shown consistent benefit. Because of the rarity of thymic epithelial tumors, clinical trial enrollment is difficult but nevertheless essential.
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Affiliation(s)
- Tracey L Evans
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
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Palmieri G, Buonerba C, Federico P, Formisano L, Nappi L, Di Lorenzo G, Marino M, Damiano V. Everolimus plus long-acting somatostatin analogs in thymic epithelial malignancies. World J Clin Oncol 2012; 3:111-5. [PMID: 22787579 PMCID: PMC3394082 DOI: 10.5306/wjco.v3.i7.111] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Revised: 06/19/2012] [Accepted: 06/30/2012] [Indexed: 02/06/2023] Open
Abstract
Although thymic epithelial tumors (TETs) are rare in the general population, they represent the most frequently diagnosed primary malignant tumor of the anterior mediastinum. Unlike localized disease, metastatic disease is invariably fatal. While several chemotherapy agents have proven to be effective in TETs, somatostatin analogs are the only targeted agents with an established role in this disease. Everolimus is an mTOR inhibitor with multiple application in oncology. In this report, we show for the first time that everolimus was effective in two heavily pretreated patients with advanced TETs, with a progression-free survival longer than 1 year and minimal toxicity.
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Affiliation(s)
- Giovannella Palmieri
- Clinical Endocrinology and Oncology Department, UniversityFederico II, Via Pansini 5, 80128 Naples,Italy.
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Kelly RJ, Petrini I, Rajan A, Wang Y, Giaccone G. Thymic malignancies: from clinical management to targeted therapies. J Clin Oncol 2011; 29:4820-7. [PMID: 22105817 PMCID: PMC3675690 DOI: 10.1200/jco.2011.36.0487] [Citation(s) in RCA: 105] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Accepted: 08/03/2011] [Indexed: 12/14/2022] Open
Abstract
PURPOSE A key challenge in the treatment of thymoma and thymic carcinoma (TC) is in improving our understanding of the molecular biology of these relatively rare tumors. In recent years, significant efforts have been made to dissect the molecular pathways involved in their carcinogenesis. Here we discuss the results of large-scale genomic analyses conducted to date and review the most active chemotherapies and targeted treatments. METHODS We reviewed the literature for chemotherapeutic trials in the last 20 years and trials involving targeted therapies between 1999 and 2010. The search was supplemented by a review of abstracts presented at the annual meetings of the American Society of Clinical Oncology (from 1999 to 2010), at the first International Conference on Thymic Malignancies in 2009, and at a follow-up meeting of the newly formed International Thymic Malignancies Interest Group in 2010. RESULTS Surgery remains the treatment of choice for operable tumors, whereas chemotherapy is standard in locally advanced and metastatic disease. Thus far, targeted therapies have been developed empirically. Histone deacetylase inhibitors have shown some activity in thymoma whereas sunitinib may be active in TC. There are no data to support the use of HER2- or EGFR-targeted therapies in thymic malignancies. CONCLUSION Drug development for the treatment of thymic malignancies is difficult because of the rarity of these tumors. Ethnic differences are becoming apparent, with aggressive subtypes being observed in Asians and African Americans. Incremental improvements in our understanding of tumor biology suggest that molecular profiling-directed therapies may be the preferred route of investigation in the future.
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Affiliation(s)
- Ronan J. Kelly
- All authors: National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Iacopo Petrini
- All authors: National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Arun Rajan
- All authors: National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Yisong Wang
- All authors: National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Giuseppe Giaccone
- All authors: National Cancer Institute, National Institutes of Health, Bethesda, MD
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