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一名肺低分化腺癌患者中新型双融合的共存及对阿来替尼的反应:病例报告与文献综述

Coexistence of a novel , double-fusion in a lung poorly differentiated adenocarcinoma patient and response to alectinib: a case report and literature review.

作者信息

Chen Huang, Zhang Menglan, Bai Liyan, Niu Yun, Wang Xiaowei, Jiang Ruiying, Wang Ye, Feng Qianqian, Wang Bei, Dai Tingli, Yuan Mingming, Chen Rongrong, Qi Yujuan, Zhong Dingrong

机构信息

Department of Pathology, China-Janpan Friendship Hospital, Beijing, China.

Department of Pathology, Qinghai Provincial People's Hospital, Xining, China.

出版信息

Front Oncol. 2024 Dec 13;14:1453259. doi: 10.3389/fonc.2024.1453259. eCollection 2024.

Abstract

BACKGROUND

Anaplastic lymphoma kinase () rearrangement, the most common oncogenic rearrangement in lung adenocarcinoma, occurs in approximately 5% of non-small cell lung cancer (NSCLC) patients. gene is the most common partner of rearrangement, and distinct EML4-ALK fusions differ in their responsiveness to ALK tyrosine kinase inhibitors. However, the concurrence of two rearrangements in one patient and whose response to ALK-TKIs have rarely been reported so far.

CASE PRESENTATION

A 47-year-old Chinese male was diagnosed with stage IV lung adenocarcinoma with multiple intracranial metastases and adrenal metastasis. After progression of two lines of chemotherapy combined with local radiotherapy regimens, his tumor tissue sample was sent to perform the DNA-based next-generation sequencing of 116 genes. Surprisingly, (E13:A20) fusion and a novel (S6:A20) fusion were concurrently identified, which was confirmed using immunohistochemistry and fluorescence hybridization. Given the superior efficacy of alectinib, the patient received alectinib in the third-line setting with the progression-free survival over 14 months up to now. Moreover, through comprehensive review of previous literatures, a total of 22 patients with multiple fusions and their response to ALK-TKIs were summarized.

CONCLUSION

This is the first report of a NSCLC patient with a novel , double-fusion benefiting from alectinib. Alectinib may be an effective therapeutic option for both primary and metastatic lesions including brain metastases in the late-line setting in NSCLC patients with double- fusion.

摘要

背景

间变性淋巴瘤激酶(ALK)重排是肺腺癌中最常见的致癌重排,约5%的非小细胞肺癌(NSCLC)患者会发生。EML4基因是ALK重排最常见的伙伴,不同的EML4-ALK融合对ALK酪氨酸激酶抑制剂的反应性不同。然而,一名患者同时出现两种ALK重排及其对ALK-TKIs反应的情况,目前鲜有报道。

病例介绍

一名47岁中国男性被诊断为IV期肺腺癌伴多发颅内转移和肾上腺转移。在两线化疗联合局部放疗方案进展后,其肿瘤组织样本被送去进行116个基因的基于DNA的二代测序。令人惊讶的是,同时鉴定出EML4(E13:A20)融合和一种新的EML4(S6:A20)融合,这通过免疫组化和荧光原位杂交得以证实。鉴于阿来替尼疗效卓越,该患者在三线治疗中接受了阿来替尼,目前无进展生存期超过14个月。此外,通过全面回顾既往文献,总结了总共22例具有多种ALK融合及其对ALK-TKIs反应的患者。

结论

这是首例关于一名非小细胞肺癌患者出现新型EML4-ALK、EML4-ALK双融合并从阿来替尼治疗中获益的报道。对于双融合的非小细胞肺癌患者晚期一线治疗中包括脑转移在内的原发和转移病灶,阿来替尼可能是一种有效的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9e0/11671490/a1a56aa01d63/fonc-14-1453259-g001.jpg

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