ALK 阳性肺癌伴脑转移患者脑脊液和配对血浆中循环无细胞 DNA 的基因谱分析。

Genetic profiling of circulating cell-free DNA from cerebrospinal fluid and paired plasma in ALK-positive lung cancer with brain metastases.

机构信息

Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

出版信息

Thorac Cancer. 2023 Jul;14(19):1883-1893. doi: 10.1111/1759-7714.14936. Epub 2023 Jun 7.

BACKGROUND

This study used next-generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors.

METHODS

From January 2016 to January 2021, 19 non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK-positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168-gene panel. The intracranial response and prognosis were also investigated.

RESULTS

The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK-positive patients. ALK-positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK-positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression-free survival was 8.0 and 18.0 months for ALK-positive (n = 5) and ALK-negative (n = 14), respectively (p = 0.077).

CONCLUSION

CSF may serve as a liquid biopsy for ALK-positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes.

背景

本研究采用下一代测序（NGS）技术检测脑脊液（CSF）、血浆和肿瘤组织中的遗传谱，探索检测间变性淋巴瘤激酶（ALK）重排状态的替代方法和 ALK 抑制剂潜在耐药机制。

方法

2016 年 1 月至 2021 年 1 月，北京胸科医院共纳入 19 例有脑转移（BM）和 ALK 阳性原发性肿瘤的非小细胞肺癌（NSCLC）患者。采用包含 168 个基因的 19 例 NSCLC 伴脑转移患者的 CSF、血浆和原发肿瘤样本进行 NGS 检测。同时还对颅内反应和预后进行了研究。

结果

本研究共纳入 19 例患者，7 例女性，12 例男性，年龄 29 至 68 岁（中位年龄 44 岁）。所有病例的 CSF 细胞学均为阴性。NGS 结果显示，26.3%（5/19）的 CSF cfDNA 样本、78.9%（15/19）的血浆样本和 89.5%（17/19）的 ALK 阳性患者肿瘤样本中检测到 ALK 融合基因。ALK 阳性 CSF 样本的 CSF cfDNA 中 ALK 等位基因分数明显高于其他两种样本类型。在 5 例 CSF 中 ALK 阳性的患者中，在接受 ALK 抑制剂±局部治疗后，1 例患者颅内完全缓解，2 例患者颅内部分缓解。ALK 阳性（n=5）和 ALK 阴性（n=14）患者 CSF 样本的颅内中位无进展生存期分别为 8.0 和 18.0 个月（p=0.077）。