Zheng H, Zhao D, Gu M, Wang Q H, Li C H, Li X, Li J, Che N Y, Hu Y
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Zhonghua Yi Xue Za Zhi. 2024 Oct 29;104(40):3751-3756. doi: 10.3760/cma.j.cn112137-20240422-00952.
To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%: 7.0-14.2 months), with a median OS of 8.8 months (95%: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (=0.32, 95%: 0.12-0.73, =0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%: 13.0-36.7 months). NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.
分析经表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)治疗后发生小细胞肺癌(SCLC)转化的敏感EGFR突变的非小细胞肺癌(NSCLC)患者的临床特征及预后因素。我们回顾性收集了2015年1月至2021年12月在首都医科大学附属北京胸科医院接受EGFR-TKI治疗后发生SCLC转化的21例晚期EGFR突变NSCLC患者的临床资料。总结临床特征并进行预后分析。对患者随访至2024年2月。采用实体瘤疗效评价标准评估疗效,用Kaplan-Meier法绘制生存曲线,采用log-rank检验比较转化型SCLC患者局限期与广泛期生存时间(OS)的差异。采用Cox比例风险模型分析SCLC转化后生存的影响因素。21例患者中,男性5例,女性16例,年龄33~74岁[(58.9±2.6)岁]。21例患者均为具有敏感EGFR突变的腺癌。EGFR基因19del突变18例(85.7%),其中1例为19del+间变性淋巴瘤激酶(ALK)突变,3例为L858R突变。转化后的SCLC中,单纯SCLC 11例,混合性SCLC(腺癌和小细胞癌成分共存)10例。从NSCLC诊断到SCLC转化的中位时间为12.0个月(95%:7.6~16.3个月)。21例SCLC转化患者中,广泛期13例,局限期8例。其中16例患者接受了以依托泊苷为基础的全身化疗,其中13例可评估疗效,11例可计算无进展生存期(PFS)。5例部分缓解,5例稳定,3例疾病进展,3例无法评估。中位无进展生存时间(PFS)为4.8个月(95%:2.8~6.8个月)。21例患者SCLC转化后的中位生存时间(OS)为10.6个月(95%:7.0~14.2个月),广泛期患者的中位OS为8.8个月(95%:6.3~11.4个月),局限期患者为27.5个月(95%:9.6~34.4个月),差异有统计学意义(P=0.002)。Cox比例风险模型分析显示,SCLC转化后的局限期是OS的保护因素(P=0.32,95%:0.12~0.73,P=0.010)。21例患者从肺癌诊断开始的中位OS为24.9个月(95%:13.0~36.7个月)。发生SCLC转化的NSCLC患者均为腺癌,EGFR19del突变比例相对较高。SCLC转化后,一般采用SCLC的标准化疗方案进行治疗。SCLC转化后的OS与分期有关,局限期预后较好。