Chengzhi Cai1, Yuan Tang2, Yanying Li3, Yuqi Chen4, Panwen Tian5, Yongsheng Wang6, Youling Gong7, Feng Peng8, Yan Zhang9, Min Yu10, Ke Wang11, Jiang Zhu12, You Lu13, Meijuan Huang14. 1. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: ml63729366@gmail.com. 2. Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: 1202ty@163.com. 3. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: liyanying2001@163.com. 4. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: wcmscyq@gmail.com. 5. Department of Respiratory, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: mrascend@163.com. 6. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: wangy756@163.com. 7. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: gongyouling@hotmail.com. 8. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: pfwork@126.com. 9. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: zhangyan915@126.com. 10. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: yuminisagoodgirl@163.com. 11. Department of Respiratory, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: 442620720@qq.com. 12. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: hxnadal@163.com. 13. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: radyoulu@hotmail.com. 14. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: hmj107@163.com.
Abstract
INTRODUCTION: Patients with ALK rearranged non-small-cell lung cancer (NSCLC) show survival benefits from tyrosine-kinase inhibitor (TKI). Widely application of DNA sequencing revealed various rearrangement pattern in addition to single EML4-ALK fusion. Here, we retrospectively analyzed the distribution and coexistence of ALK rearrangement and therapeutic outcome of patients with ALK rearranged NSCLC. METHOD: ALK positive NSCLC patients were screened at West China Hospital. NGS was performed on pre-treatment samples. Clinical characteristics and therapeutic outcomes were collected to retrospectively analyzed. RESULTS: Among the 89 patients with 22 ALK rearrangements, fusions of intergenic sequences with ALK were found in 15 (16.85 %). Non-EML4-ALK fusions were present in 18 patients (20.22 %). Coexistence of rearrangements were present in 16 patients (17.98 %). Intergenic sequence-ALK and non-EML4-ALK fusions occurred at higher rates in patients with at least two fusions (62.5 % versus 6.85 % for intergenic sequence-ALK, 62.5 % versus 10.96 % for non-EML4-ALK). There were 40 ALK-rearranged NSCLC patients receiving the first-line crizotinib. The median progression-free survival (PFS) was 9.7 months when excluding three lost patients. In the seven patients who had at least two fusions, the median PFS was 11.9 months, compared with 9.0 months among those with single (p = 0.336). No significant difference in median PFS was found between patients with and without intergenic-ALK fusion (12.0 months versus 9.6 months, p = 0.989). The median PFS was 9.0 months in patients harboring a single EML4-ALK fusion versus 13.0 months in those with other ALK alterations (P = 0.890). The PFS of patients with single intergenic sequence-ALK fusion reached to 2.9 months, 27 months, and 28.9 months respectively. CONCLUSION: Our study reports the distribution of intergenic sequence-ALK and coexisting fusions in ALK-rearranged NSCLC. Intergenic sequence-ALK and non-EML4-ALK are prone to coexist with other fusions. Neither intergenic sequence-ALK nor coexistence of fusions had a significant effect on the therapeutic benefit of treatment with crizotinib.
INTRODUCTION:Patients with ALK rearranged non-small-cell lung cancer (NSCLC) show survival benefits from tyrosine-kinase inhibitor (TKI). Widely application of DNA sequencing revealed various rearrangement pattern in addition to single EML4-ALK fusion. Here, we retrospectively analyzed the distribution and coexistence of ALK rearrangement and therapeutic outcome of patients with ALK rearranged NSCLC. METHOD:ALK positive NSCLCpatients were screened at West China Hospital. NGS was performed on pre-treatment samples. Clinical characteristics and therapeutic outcomes were collected to retrospectively analyzed. RESULTS: Among the 89 patients with 22 ALK rearrangements, fusions of intergenic sequences with ALK were found in 15 (16.85 %). Non-EML4-ALK fusions were present in 18 patients (20.22 %). Coexistence of rearrangements were present in 16 patients (17.98 %). Intergenic sequence-ALK and non-EML4-ALK fusions occurred at higher rates in patients with at least two fusions (62.5 % versus 6.85 % for intergenic sequence-ALK, 62.5 % versus 10.96 % for non-EML4-ALK). There were 40 ALK-rearranged NSCLCpatients receiving the first-line crizotinib. The median progression-free survival (PFS) was 9.7 months when excluding three lost patients. In the seven patients who had at least two fusions, the median PFS was 11.9 months, compared with 9.0 months among those with single (p = 0.336). No significant difference in median PFS was found between patients with and without intergenic-ALK fusion (12.0 months versus 9.6 months, p = 0.989). The median PFS was 9.0 months in patients harboring a single EML4-ALK fusion versus 13.0 months in those with other ALK alterations (P = 0.890). The PFS of patients with single intergenic sequence-ALK fusion reached to 2.9 months, 27 months, and 28.9 months respectively. CONCLUSION: Our study reports the distribution of intergenic sequence-ALK and coexisting fusions in ALK-rearranged NSCLC. Intergenic sequence-ALK and non-EML4-ALK are prone to coexist with other fusions. Neither intergenic sequence-ALK nor coexistence of fusions had a significant effect on the therapeutic benefit of treatment with crizotinib.
Authors: Yinghuan Dai; Ping Liu; Wenlong He; Lizhen Yang; Yang Ni; Xuejiao Ma; Furong Du; Chao Song; Yang Liu; Yi Sun Journal: Front Oncol Date: 2022-06-16 Impact factor: 5.738