Xu Xinyan, Liu Di, Wen Junmiao, Chen Jiayan, Fan Min
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Transl Lung Cancer Res. 2020 Dec;9(6):2500-2507. doi: 10.21037/tlcr-20-1212.
Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion occurs in approximately 5% of non-small cell lung cancer (NSCLC) cases. Variants 1 and 3a/b are the most common EML4-ALK variants. Emerging evidence indicates that patients with variant 1 and those with variant 3a/b exhibit differential therapeutic responses. However, the National Comprehensive Cancer Network guidelines have not included the EML4-ALK fusion subtype in treatment decision-making to date. Herein, we report the case of a non-smoking 36-year-old female patient who was diagnosed with right lung adenocarcinoma in 2005 (cT1N3M0, IIIB) and received definitive chemoradiotherapy. The patient achieved a partial response, and her disease remained under control for 8 years. However, in May 2013, the patient was diagnosed with brain metastasis and underwent subsequent surgical resection, followed by postoperative brain radiotherapy and chemotherapy. Postoperative pathology confirmed ALK gene rearrangement, and next-generation sequencing performed in 2020 identified the EML4-ALK variant as variant 1. After progression-free survival lasting 4 years, new metastatic lesions were found in the patient's right lung, and she was administered crizotinib for 20 months. Due to a suspicious recurrence in the intracranial surgical margin area, as well as an unbearable gastrointestinal reaction to crizotinib, alectinib was later adopted. At the 7-month follow-up, positron emission tomography/computed tomography revealed a clinical complete response. This case of an NSCLC patient with EML4-ALK fusion variant 1 who exhibited an exceptional response to chemoradiotherapy and ALK inhibitors might broaden horizons in efforts to reveal the molecular mechanism of radiosensitivity in ALK-positive NSCLC and provide reference for further research regarding the optimal radiotherapy delivery dose and tyrosine kinase inhibitor selection.
棘皮动物微管相关蛋白样4（EML4）-间变性淋巴瘤激酶（ALK）融合在约5%的非小细胞肺癌（NSCLC）病例中出现。变体1和3a/b是最常见的EML4-ALK变体。新出现的证据表明，变体1患者和变体3a/b患者表现出不同的治疗反应。然而，美国国立综合癌症网络指南迄今尚未将EML4-ALK融合亚型纳入治疗决策中。在此，我们报告一例36岁非吸烟女性患者的病例，该患者于2005年被诊断为右肺腺癌（cT1N3M0，IIIB期）并接受了根治性放化疗。患者达到部分缓解，其疾病得到控制达8年。然而，2013年5月，该患者被诊断为脑转移并随后接受了手术切除，接着进行了术后脑部放疗和化疗。术后病理证实ALK基因重排，2020年进行的二代测序确定EML4-ALK变体为变体1。在无进展生存4年后，患者右肺发现新的转移灶，她接受了20个月的克唑替尼治疗。由于颅内手术切缘区域可疑复发，以及对克唑替尼难以忍受的胃肠道反应，后来采用了阿来替尼。在7个月的随访中，正电子发射断层扫描/计算机断层扫描显示临床完全缓解。该例携带EML4-ALK融合变体1的NSCLC患者对放化疗和ALK抑制剂表现出异常反应，这可能会拓宽揭示ALK阳性NSCLC放射敏感性分子机制的研究视野，并为进一步研究最佳放疗剂量和酪氨酸激酶抑制剂选择提供参考。
