Wang Zirong, Shi Yu, Zhang Peng, Chen Yuan
Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Chin Clin Oncol. 2023 Dec;12(6):70. doi: 10.21037/cco-23-111.
Anaplastic lymphoma kinase (ALK) rearrangement generates an oncogenic ALK tyrosine kinase that activates numerous downstream signaling pathways, leading to increased cell proliferation and survival. About 5% of non-small cell lung cancer (NSCLC) patients are being diagnosed with tumor harboring ALK-positive. ALK rearrangement is an important molecular target for the treatment of NSCLC, and alectinib is a potent and highly selective second-generation ALK inhibitor. Alectinib as a neoadjuvant therapy has been reported in previous studies. However, cases of patients undergoing left total pulmonary resection after neoadjuvant therapy are rare.
In this report, a 52-year-old Asian woman's chest computed tomography (CT) showed mass shadows in the left lung. Echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion variant was detected by next-generation sequencing. We administered the targeted drug alectinib at 600 mg twice daily for two and a half months. Positron emission tomography (PET)-CT examination showed that the left lung mass and lymph nodes were significantly reduced. The tumor node metastasis (TNM) stage was reduced from cT4N2M0, IIIb to ycT2aN0M0, IB. Then she underwent thoracoscopic transthoracotomy of the left total lung. Oral alectinib therapy was continued after surgery, and the follow-up duration was one year.
This case indicates that alectinib is feasible and has a good safety profile as a neoadjuvant therapy for ALK-positive NSCLC. But further research is needed to determine how long the treatment should last for patients to get the most benefit. There is also the problem of pulmonary fibrosis in the process of alectinib neoadjuvant therapy, which needs to be solved urgently.
间变性淋巴瘤激酶(ALK)重排产生一种致癌的ALK酪氨酸激酶,该激酶激活众多下游信号通路,导致细胞增殖和存活增加。约5%的非小细胞肺癌(NSCLC)患者被诊断为ALK阳性肿瘤。ALK重排是NSCLC治疗的重要分子靶点,阿来替尼是一种强效且高度选择性的第二代ALK抑制剂。先前的研究已报道阿来替尼作为新辅助治疗的情况。然而,新辅助治疗后接受左全肺切除术的患者病例罕见。
在本报告中,一名52岁亚洲女性的胸部计算机断层扫描(CT)显示左肺有肿块阴影。通过下一代测序检测到棘皮动物微管相关蛋白样4-ALK(EML4-ALK)融合变体。我们给予靶向药物阿来替尼,每日两次,每次600 mg,持续两个半月。正电子发射断层扫描(PET)-CT检查显示左肺肿块和淋巴结明显缩小。肿瘤淋巴结转移(TNM)分期从cT4N2M0,Ⅲb期降至ycT2aN0M0,ⅠB期。然后她接受了左全肺的胸腔镜开胸手术。术后继续口服阿来替尼治疗,随访时间为一年。
该病例表明,阿来替尼作为ALK阳性NSCLC的新辅助治疗是可行的,且安全性良好。但需要进一步研究以确定治疗持续多长时间能使患者获得最大益处。阿来替尼新辅助治疗过程中还存在肺纤维化问题,亟待解决。