Oncology Department of Beijing Chest Hospital, Capital Medical University, 9 Beiguan Street, Tongzhou District, Beijing, PR China.
Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, 17 Qihelou Street, Dongcheng District, Beijing, PR China.
BMC Pulm Med. 2023 Sep 1;23(1):319. doi: 10.1186/s12890-023-02618-x.
To analyze the characteristics and prognostic values of Anaplastic Lymphoma Kinase (ALK) fusion gene partner, gene subtype and abundance in tumor tissues of advanced Non Small Cell Lung Cancer (NSCLC) patients with positive ALK fusion gene and to explore the best treatment mode of ALK-Tyrosine Kinase Inhibitors(TKIs).
Cases of advanced NSCLC patients with ALK positive confirmed by both Next Generation Sequencing (NGS) and immunohistochemistry were retrospectively collected. The relationships of Overall Survival (OS)/Progression Free Survival (PFS) between different mutation subtypes, mutation abundance, clinicopathological features were analyzed. OS/PFS between different treatment mode of ALK inhibitors were compared.
Fifty-eight patients were enrolled. There were diverse fusion partners. Five subtypes of Echinoderm Microtubule-associated protein-Like 4 gene (EML4)-ALK fusion mutation were detected: V1,V2,V3,V5 and V7. The mutation abundance ranged from 0.13 to 27.77%, with a median of 5.34%. The abundance of V2 and V5 was higher than V1 and V3 respectively. There was no difference in OS between the low abundance group(≤ 5.34%) and the high abundance group(>5.34%) (P = 0.434). PFS of second-generation ALK inhibitors as first-line treatment was longer than that of Crizotinib as first-line (P<0.001). Never smokers had longer OS than current smokers(P = 0.001).
There are differences in abundance between different fusion partners and subtypes in advanced NSCLC with positive ALK. OS is not associated with subtypes, mutation abundance and first line treatment option of either generation of ALK inhibitors. Smoking is a poor prognostic factor.
分析晚期非小细胞肺癌（NSCLC）中具有阳性 ALK 融合基因的患者中 ANaplastic Lymphoma Kinase（ALK）融合基因伴侣、基因亚型和肿瘤组织中基因丰度的特征和预后价值，并探讨 ALK 酪氨酸激酶抑制剂（TKI）的最佳治疗模式。
回顾性收集经下一代测序（NGS）和免疫组织化学双重验证为阳性的晚期 NSCLC 患者病例。分析不同突变亚型、突变丰度、临床病理特征与总生存期（OS）/无进展生存期（PFS）的关系。比较不同 ALK 抑制剂治疗模式的 OS/PFS。
共纳入 58 例患者。融合伙伴多样化。检测到棘皮动物微管相关蛋白样 4 基因（EML4）-ALK 融合突变的 5 种亚型：V1、V2、V3、V5 和 V7。突变丰度为 0.13%~27.77%，中位数为 5.34%。V2 和 V5 的丰度分别高于 V1 和 V3。低丰度组（≤5.34%）和高丰度组（>5.34%）的 OS 无差异（P=0.434）。作为一线治疗的第二代 ALK 抑制剂的 PFS 长于作为一线治疗的克唑替尼（P<0.001）。从不吸烟者的 OS 长于现吸烟者（P=0.001）。
晚期 NSCLC 中具有阳性 ALK 的不同融合伙伴和亚型之间的丰度存在差异。OS 与亚型、突变丰度以及一代或二代 ALK 抑制剂的一线治疗方案无关。吸烟是预后不良的因素。
