Cai Chengzhi, Tang Yuan, Li Yanying, Chen Yuqi, Tian Panwen, Wang Yongsheng, Gong Youling, Peng Feng, Zhang Yan, Yu Min, Wang Ke, Zhu Jiang, Lu You, Huang Meijuan
Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China.
Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China.
Lung Cancer. 2021 Feb;152:104-108. doi: 10.1016/j.lungcan.2020.12.018. Epub 2021 Jan 9.
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.
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.
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.
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.
间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）患者可从酪氨酸激酶抑制剂（TKI）治疗中获益。除了单一的棘皮动物微管相关蛋白样4（EML4）-ALK融合外，DNA测序的广泛应用揭示了各种重排模式。在此，我们回顾性分析了ALK重排的NSCLC患者中ALK重排的分布和共存情况以及治疗结果。
在中国西部医院筛查ALK阳性的NSCLC患者。对治疗前样本进行二代测序（NGS）。收集临床特征和治疗结果进行回顾性分析。
在89例有22种ALK重排的患者中，发现15例（16.85%）存在基因间序列与ALK的融合。18例患者（占20.22%）存在非EML4-ALK融合。16例患者（占17.98%）存在重排共存。在至少有两种融合的患者中，基因间序列-ALK和非EML4-ALK融合的发生率更高（基因间序列-ALK为62.5%对6.85%，非EML4-ALK为62.5%对10.96%）。有40例ALK重排的NSCLC患者接受了一线克唑替尼治疗。排除3例失访患者后，中位无进展生存期（PFS）为9.7个月。在7例至少有两种融合的患者中，中位PFS为11.9个月，而单一融合患者为9.0个月（p = 0.336）。有和没有基因间ALK融合的患者中位PFS无显著差异（分别为12.0个月对9.6个月，p = 0.989）。携带单一EML4-ALK融合的患者中位PFS为9.0个月，而有其他ALK改变的患者为13.0个月（P = 0.890）。单一基因间序列-ALK融合患者的PFS分别达到2.9个月、27个月和28.9个月。
我们的研究报告了ALK重排的NSCLC中基因间序列-ALK和共存融合的分布情况。基因间序列-ALK和非EML4-ALK容易与其他融合共存。基因间序列-ALK和融合共存对克唑替尼治疗的获益均无显著影响。
