转化性小细胞肺癌患者的基因组分析、风险分层和转化后治疗结局：一项多中心分析
Genomic Profiling, Risk Stratification, and Post-Transformation Treatment Outcomes in Patients with Transformed Small-Cell Lung Cancer: A Multicenter Analysis.
作者
作者单位
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, 250117, China.
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
- Department of Respiratory Medicine, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, TaiYuan, ShanXi 030013, China.
- Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Tianwen Avenue No. 288, Nan'an District, Chongqing 400010, China.
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: zhong-jia817@163.com.
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: zlhuxi@163.com.
摘要
中文
转化性小细胞肺癌（T-SCLC）是EGFR突变肺腺癌中日益被认识的耐药机制。本研究旨在识别组织学转化的早期预测因素并评估转化后的治疗结局。我们回顾性收集了来自五个中国中心的163例T-SCLC患者。对60例EGFR突变患者进行了二代测序，包括47对原发-转化配对样本。进行了整合的基因组和临床分析以描绘分子特征和生存结局。在150例EGFR突变患者中，至SCLC转化的中位时间为25.8个月，转化后中位总生存期（OS）为14.2个月。鉴于样本量有限，对13例EGFR野生型患者的临床和生存数据进行了描述性报告。在108例可评估治疗的患者中，一线EGFR-TKI联合化疗、单纯化疗和免疫检查点抑制剂（ICIs）联合化疗的中位无进展生存期（PFS）分别为6.2、5.30和4.07个月（P=0.041），中位OS分别为21.2、27.6和13.6个月（P=0.193）。在后线治疗中，紫杉烷类方案的中位PFS为6.93个月，优于喜树碱类（1.13个月）和其他方案（1.90个月；P=0.049）。高进化多样性与较短的转化后OS相关（6.77 vs 11.10个月），限制性立方样条分析显示非线性的关联趋势不显著（P=0.055）。年龄、RB1/NTRK1突变和继发性T790M突变被确定为独立危险因素，并整合到高准确性的预测模型中。本研究建立了一个临床可用的模型，用于SCLC转化的早期预测和风险分层。紫杉烷类方案成为T-SCLC有前景的后线治疗选择。
English
Transformed small-cell lung cancer (T-SCLC) is an increasingly recognized resistance mechanism in EGFR-mutant lung adenocarcinoma. This study aimed to identify early predictors of histologic transformation and evaluate post-transformation treatment outcomes. We retrospectively collected 163 T-SCLC patients from five Chinese centers. Next-generation sequencing was performed on 60 EGFR-mutant patients, including 47 paired primary-transformed samples. Integrated genomic and clinical analyses were conducted to delineate molecular features and survival outcomes. Among 150 EGFR-mutant patients, the median time to SCLC transformation was 25.8 months and median post-transformation overall survival (OS) was 14.2 months. Clinical and survival data for the 13 EGFR wild-type patients are reported descriptively given the limited sample size. Among 108 treatment-evaluable patients, first-line EGFR-TKI plus chemotherapy, chemotherapy alone, and immune checkpoint inhibitors (ICIs) plus chemotherapy yielded median progression-free survival (PFS) of 6.2, 5.30, and 4.07 months (P = 0.041) and median OS of 21.2, 27.6, and 13.6 months (P = 0.193). In later-line therapy, taxane-based regimens achieved a median PFS of 6.93 months, outperforming camptothecin-based (1.13 months) and other regimens (1.90 months; P = 0.049). High evolutionary diversity was associated with shorter post-transformation OS (6.77 vs. 11.10 months), with restricted cubic spline analysis showing a nonsignificant trend toward a nonlinear association (P = 0.055).Age, RB1/NTRK1 mutation, and secondary T790M mutation were identified as independent risk factors and integrated into a predictive model with high accuracy. This study establishes a clinically applicable model for early prediction and risk stratification of SCLC transformation. Taxane-based regimens emerge as a promising later-line therapeutic option for T-SCLC.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区