PO.CL09.03 · 临床研究
基于两个国家数据库分析的IV期大细胞肺癌的临床结局和治疗结局
Clinical outcomes and treatment outcomes of stage IV large cell lung cancer based on two national database analysis
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摘要 Abstract
中文摘要
背景：大细胞肺癌（LCLC）是非小细胞肺癌一种罕见的神经内分泌亚型，治疗选择有限且预后不良。关于IV期LCLC生存模式的证据，尤其是不同治疗方式之间的证据，仍然稀缺。本研究旨在利用两个国家队列评估临床特征、治疗模式和生存结局。
方法：从监测、流行病学和最终结果项目（SEER）17个登记处识别2000至2021年间诊断的IV期LCLC患者。符合条件的病例为根据第7版或第8版TNM分类的IV期LCLC；收集了人口学、临床病理学、社会经济学和可获得的分子数据。Kaplan-Meier分析比较了各治疗组之间的总生存期（OS）和癌症特异性生存期（CSS）：无治疗、化疗以及手术联合化疗。使用Cox比例风险模型识别CSS的独立预测因素。此外，分析了来自韩国国民健康保险系统（KNHIS）的公开可用数据，以评估表皮生长因子受体（EGFR）突变对生存的影响。
结果：共纳入3,478例患者。在SEER队列中，3年OS因治疗方式而有显著差异：无治疗为2.2%，化疗为7.1%，手术联合化疗为13.3%。CSS也观察到类似趋势。在多变量分析中，年龄>65岁（风险比（HR）1.16 [95%置信区间（CI）1.08-1.25]，p<0.0001）、男性（HR 1.17 [95% CI 1.09-1.26]，p<0.0001）和低家庭收入（HR 1.18 [95% CI 1.08-1.30]，p<0.0001）与较高的癌症相关死亡率独立相关。与单纯化疗相比，手术联合化疗降低了死亡率（HR 0.78 [95% CI 0.70-0.87]，p<0.0001）。在KNHIS队列中，666例患者中有303例（45.5%）检测到EGFR突变；然而，在接受化疗的患者中，EGFR突变的存在并未带来显著的生存获益（HR 0.821 [95% CI 0.63-1.07]，p=0.146）。
结论：尽管总体预后不良，治疗对IV期LCLC的结局有显著影响。化疗提供了明确的生存获益，而包含手术的多模式治疗提供了最大的改善，这可能反映了分子检测和靶向治疗可及性的提高。需要进一步研究——包括酪氨酸激酶抑制剂在EGFR突变疾病中的潜在获益、其他可干预突变的系统性评估，以及铂类方案后免疫治疗的持续研究——以确定这一罕见亚型的最佳管理策略。
查看英文原文 English abstract
Background: Large cell lung cancer (LCLC) is an uncommon neuroendocrine subtype of non-small cell lung cancer with limited therapeutic options and poor prognosis. Evidence regarding survival patterns in stage IV LCLC, particularly across different treatment modalities, remains scarce. This study aimed to evaluate clinical characteristics, treatment patterns, and survival outcomes using two national cohorts.
Methods: Patients with stage IV LCLC diagnosed between 2000 and 2021 were identified from the Surveillance, Epidemiology, and End Results Program (SEER) 17 registries. Eligible cases were stage IV LCLC according to the 7th or 8th TNM classification; demographic, clinicopathologic, socioeconomic, and available molecular data were collected. Kaplan-Meier analyses compared overall survival (OS) and cancer-specific survival (CSS) across treatment groups: no treatment, chemotherapy, and combined surgery plus chemotherapy. Cox proportional hazards models were used to identify independent predictors of CSS. In addition, publicly available data from the Korean National Health Insurance System (KNHIS) were analyzed to assess the impact of epidermal growth factor receptor (EGFR) mutation on survival.
Results: A total of 3,478 patients were included. In the SEER cohort, 3-year OS differed substantially by treatment modality: 2.2% with no treatment, 7.1% with chemotherapy, and 13.3% with surgery plus chemotherapy. Similar trends were observed for CSS. In multivariable analysis, age >65 years (hazard ratio (HR) 1.16 [95% confidence interval (CI) 1.08-1.25], p<0.0001), male sex (HR 1.17[95% CI 1.09-1.26], p<0.0001), and low household income (HR 1.18[95% CI 1.08-1.30], p<0.0001) were independently associated with higher cancer-related mortality. Compared with chemotherapy alone, surgery combined with chemotherapy reduced mortality (HR 0.78[95% CI 0.70-0.87], p<0.0001). Among the KNHIS cohort, EGFR mutations were detected in 303 of 666 patients (45.5%); however, the presence of EGFR mutation did not confer a significant survival benefit among patients who received chemotherapy (HR 0.821 [95% CI 0.63-1.07], p=0.146).
Conclusions: Despite the overall poor prognosis, treatment significantly influences outcomes in stage IV LCLC. Chemotherapy provides a clear survival benefit, and multimodal therapy that includes surgery offers the greatest improvement, potentially reflecting increased access to molecular testing and targeted therapy. Further investigation- including the potential benefits of tyrosine-kinase inhibitors in EGFR-mutated disease, systematic evaluation of other actionable mutations, and ongoing studies of immunotherapy after platinum-based regimens- is needed to define optimal management strategies for this rare subtype.
利益披露 Disclosure
W. Woo, None..
S. Kim, None..
J. Kim, None..
V. Lopez, None..
K. Chohan, None..
D. Thota, None..
Y. Lee, None..
C. Wong, None..
A. Savadkar, None..
D. Moon, None..
S. Lee, None.