Expert consensus on the diagnosis and treatment of RET gene fusion non‐small cell lung cancer in China

Author:

Pu Xingxiang1,Xu Chunwei23ORCID,Wang Qian4,Wang Wenxian5ORCID,Wu Fang6ORCID,Cai Xiuyu7,Song Zhengbo5ORCID,Yu Jinpu8,Zhong Wenzhao9ORCID,Wang Zhijie10,Zhang Yongchang11ORCID,Liu Jingjing12,Zhang Shirong13ORCID,Liu Anwen14,Li Wen15,Zhan Ping3ORCID,Liu Hongbing3ORCID,Lv Tangfeng3ORCID,Miao Liyun16ORCID,Min Lingfeng17,Lin Gen18ORCID,Huang Long14ORCID,Yuan Jingping19,Jiang Zhansheng20ORCID,Rao Chuangzhou21,Lv Dongqing22,Yu Zongyang23,Li Xiaoyan24,Tang Chuanhao25,Zhou Chengzhi26ORCID,Zhang Junping27,Guo Hui28,Chu Qian29,Meng Rui30,Liu Xuewen31,Wu Jingxun32,Zhou Jin33,Zhu Zhengfei34ORCID,Pan Weiwei35,Pang Fei36,Huang Jintao36,Wang Kai36,Wu Fan37,Shen Tingting38,Zou Shirui38,Xu Bingwei39,Wang Liping40,Zhu Youcai41,Lin Xinqing26ORCID,Cai Jing14ORCID,Xu Ling42,Li Jisheng43ORCID,Jiao Xiaodong44,Li Kainan45,Feng Huijing27,Wang Lin46,Du Yingying47ORCID,Yao Wang48,Shi Xuefei49,Niu Xiaomin50,Yuan Dongmei3,Yao Yanwen3,Kang Jing9,Zhang Jiatao9,Zhang Chao9,Fu Jianfei51,Huang Jianhui52,Zhang Yinbin53,Sun Pingli54,Wang Hong55,Ye Mingxiang3,Wang Dong3,Wang Zhaofeng3,Hao Yue5ORCID,Wang Zhen56,Wan Bing57,Lv Donglai58ORCID,Lan Gang41,Yang Shengjie59,Shi Lin60,Wang Yina61,Li Bihui62,Zhang Zhang63,Li Zhongwu64,Li Yuan65,Liu Zhefeng55,Yang Nong11,Wang Huijuan66,Huang Wenbin67,Hong Zhuan68,Wang Guansong69,Wang Jiandong70,Fang Meiyu5,Fang Yong71,Zhu Xixu56,Shen Yi72ORCID,Zhang Yiping5,Ma Shenglin73,Song Yong3ORCID,Lu Yuanzhi74ORCID,Fang Wenfeng75,Li Ziming50,Wu Lin1

Affiliation:

1. The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Central South University Changsha People's Republic of China

2. Institute of Cancer and Basic Medicine (ICBM) Chinese Academy of Sciences Hangzhou People's Republic of China

3. Department of Respiratory Medicine, Affiliated Jinling Hospital Medical School of Nanjing University Nanjing People's Republic of China

4. Department of Respiratory Medicine Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing People's Republic of China

5. Department of Chemotherapy Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital) Hangzhou People's Republic of China

6. Department of Oncology, The Second Xiangya Hospital Central South University Changsha People's Republic of China

7. Department of VIP Inpatient, 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

8. Department of Cancer Molecular Diagnostics Core Tianjin Medical University Cancer Institute and Hospital Tianjin People's Republic of China

9. 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

10. State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing People's Republic of China

11. 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

12. Department of Thoracic Cancer Jilin Cancer Hospital Jilin People's Republic of China

13. 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

14. Department of Oncology Second Affiliated Hospital of Nanchang University Nanchang People's Republic of China

15. Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Cancer Center Zhejiang University Hangzhou People's Republic of China

16. Department of Respiratory Medicine, Affiliated Drum Tower Hospital Medical School of Nanjing University Nanjing People's Republic of China

17. Department of Respiratory Medicine Clinical Medical School of Yangzhou University, Subei People's Hospital of Jiangsu Province Yangzhou People's Republic of China

18. Department of Medical Oncology Fujian Medical University Cancer Hospital & Fujian Cancer Hospital Fuzhou People's Republic of China

19. Department of Pathology Renmin Hospital of Wuhan University Wuhan People's Republic of China

20. Department of Integrative Oncology Tianjin Medical University Cancer Institute and Hospital Tianjin People's Republic of China

21. Department of Radiotherapy and Chemotherapy, Hwamei Hospital University of Chinese Academy of Sciences Ningbo People's Republic of China

22. Department of Pulmonary Medicine Taizhou Hospital of Wenzhou Medical University Taizhou People's Republic of China

23. 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

24. Department of Oncology, Beijing Tiantan Hospital Capital Medical University Beijing People's Republic of China

25. Department of Medical Oncology Peking University International Hospital Beijing People's Republic of China

26. 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

27. Department of Thoracic Oncology, Shanxi Academy of Medical Sciences Shanxi Bethune Hospital Taiyuan People's Republic of China

28. Department of Medical Oncology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an People's Republic of China

29. Department of Oncology, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of China

30. Cancer Center, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of China

31. Department of Oncology, the Third Xiangya Hospital Central South University Changsha People's Republic of China

32. Department of Medical Oncology, the First Affiliated Hospital of Medicine Xiamen University Xiamen People's Republic of China

33. 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

34. Department of Radiation Oncology Fudan University Shanghai Cancer Center Shanghai People's Republic of China

35. Department of Cell Biology, College of Medicine Jiaxing University Jiaxing People's Republic of China

36. Department of Medical Shanghai OrigiMed Co, Ltd Shanghai People's Republic of China

37. Department of Medical Menarini Silicon Biosystems Spa Shanghai People's Republic of China

38. Department of Medical Stone Pharmaceuticals (Suzhou) Co., Ltd. Shanghai People's Republic of China

39. Department of Biotherapy, Cancer Institute First Affiliated Hospital of China Medical University Shenyang People's Republic of China

40. Department of Oncology Baotou Cancer Hospital Baotou People's Republic of China

41. Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital The Third Affiliated Hospital of Jiaxing University Jiaxing People's Republic of China

42. Department of Interventional Pulmonary Diseases Anhui Chest Hospital Hefei People's Republic of China

43. Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinnan People's Republic of China

44. Department of Medical Oncology, Shanghai Changzheng Hospital Naval Medical University Shanghai People's Republic of China

45. Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine Shandong University Jinan People's Republic of China

46. Department of Pathology, Shanxi Academy of Medical Sciences Shanxi Bethune Hospital Taiyuan People's Republic of China

47. Department of Oncology The First Affiliated Hospital of Anhui Medical University Hefei People's Republic of China

48. Department of Interventional Oncology, The First Affiliated Hospital Sun Yat‐sen University Guangzhou People's Republic of China

49. Department of Respiratory Medicine, Huzhou Hospital Zhejiang University School of Medicine Huzhou People's Republic of China

50. Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai People's Republic of China

51. Department of Medical Oncology, Affiliated Jinhua Hospital Zhejiang University School of Medicine Jinhua People's Republic of China

52. Department of Oncology Lishui Municipal Central Hospital Lishui People's Republic of China

53. Department of Oncology, the Second Affiliated Hospital of Medical College Xi'an Jiaotong University Xi'an People's Republic of China

54. Department of Pathology The Second Hospital of Jilin University Changchun People's Republic of China

55. Senior Department of Oncology The 5th Medical Center of PLA General Hospital Beijing People's Republic of China

56. Department of Radiation Oncology, Affiliated Jinling Hospital Medical School of Nanjing Nanjing People's Republic of China

57. Department of Respiratory Medicine The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing People's Republic of China

58. Department of Clinical Oncology The 901 Hospital of Joint Logistics Support Force of People Liberation Army Hefei People's Republic of China

59. Department of Thoracic Surgery Chuxiong Yi Autonomous Prefecture People's Hospital Chuxiong People's Republic of China

60. Department of Respiratory Medicine, Zhongshan Hospital Fudan University Shanghai People's Republic of China

61. Department of Oncology, The First Affiliated Hospital, College of Medicine Zhejiang University Hangzhou People's Republic of China

62. Department of Oncology The Second Affiliated Hospital of Guilin Medical University Guilin People's Republic of China

63. International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy Jinan University Guangzhou People's Republic of China

64. 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

65. Department of Pathology Fudan University Shanghai Cancer Center Shanghai People's Republic of China

66. Department of Medical Oncology The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Zhengzhou People's Republic of China

67. Department of Pathology the First Affiliated Hospital of Henan University of Science and Technology Luoyang People's Republic of China

68. Department of Medical Oncology, Jiangsu Cancer Hospital Nanjing Medical University Affiliated Cancer Hospital Nanjing People's Republic of China

69. Institute of Respiratory Diseases, Xinqiao Hospital Third Military Medical University Chongqing People's Republic of China

70. Department of Pathology, Affiliated Jinling Hospital Medical School of Nanjing University Nanjing People's Republic of China

71. Department of Medical Oncology, Sir Run Run Shaw Hospital Zhejiang University Hangzhou People's Republic of China

72. Department of Thoracic Surgery, Affiliated Jinling Hospital Medical School of Nanjing University Nanjing People's Republic of China

73. 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

74. Department of Clinical Pathology The First Affiliated Hospital of Jinan University Guangzhou People's Republic of China

75. 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

Abstract

AbstractThe rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Publisher

Wiley

Subject

Pulmonary and Respiratory Medicine,Oncology,General Medicine

Reference69 articles.

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