Reconsidering the Cutoff Value for Sensitive and Refractory Relapses in Extensive-Stage SCLC in the Era of Immunotherapy
Reconsidering the Cutoff Value for Sensitive and Refractory Relapses in Extensive-Stage SCLC in the Era of Immunotherapy
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DOI：
10.1016/j.jtho.2023.09.1446
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发表时间：
2024-02-05
影响因子：
20.4
通讯作者：
Ohe，Yuichiro
中科院分区：
文献类型：
--
作者：
Torasawa，Masahiro;Horinouchi，Hidehito;Ohe，Yuichiro
传统上，复发的小细胞肺癌根据最后一次化疗和疾病进展之间的临界值(60天或90天)被归类为“敏感”或“难治”。然而，这些临界值并不是从严格的分析方法中得出的，它们在当代治疗中的适用性仍然不确定。方法我们对在联合免疫治疗获得批准之前(ICI前队列)和(ICI后队列)批准联合免疫治疗之前(ICI前队列)和(ICI后队列)批准联合免疫治疗之前(ICI前队列)和(ICI后队列)接受二线治疗的广泛期小细胞肺癌患者进行了回顾性多中心研究。在二线总体生存的多变量Cox回归模型中，我们选择了双侧dp值最低的最佳无铂区间截断值。采用双重交叉验证对所选临界值的内部效度进行评估。结果ICI前和ICI后队列中分别有235名和98名患者。在脑梗塞前队列中，最佳截止时间为59天(p=0.0001)；采用双重交叉验证计算的危险比为1.31(95%可信区间：0.95-1.82)。在脑梗塞后的队列中，尽管60天和90天的临界值可以预测预后(60天；p=0.002，90天；结论明确了以往对小细胞肺癌复发分类的模糊分界值，发现75天的分界值比传统的分界值更能准确地预测复发后的预后。
IntroductionTraditionally, relapsed SCLC has been classified as “sensitive” or “refractory” on the basis of cutoff values (60 or 90 d) for the duration between the last chemotherapy and disease progression. Nevertheless, these cutoff values are not derived from rigorous analytical methods, and their applicability to contemporary treatments remains uncertain.MethodsWe conducted a retrospective multicenter study on patients with extensive-stage SCLC who underwent second-line therapy after platinum-doublet chemotherapy with or without immune checkpoint inhibitor (ICI) resistance before (pre-ICI cohort) and after (post-ICI cohort) approval of combination immunotherapy. We selected the optimal platinum-free interval cutoff value with the lowest two-sidedpvalue in the multivariable Cox regression model for second-line overall survival. The internal validity of the chosen cutoff value was assessed using twofold cross-validation.ResultsThere were 235 and 98 patients in the pre-ICI and post-ICI cohorts, respectively. In the pre-ICI cohort, the optimal cutoff was 59 days (p= 0.0001); the hazard ratio calculated using twofold cross-validation was 1.31 (95% confidence interval: 0.95–1.82]). In the post-ICI cohort, although the 60- and 90-day cutoff values could predict prognosis (60 d;p= 0.002, 90 d;p= 0.005), the optimal cutoff value was 75 days (p= 0.0002), which resulted in a median second-line overall survival of 15.9 and 5.0 months for patients with sensitive and refractory relapse, respectively (hazard ratio = 2.77, 95% confidence interval: 1.56–4.93).ConclusionsWe clarified the previously ambiguous cutoff values for classifying relapsed SCLC and revealed that the 75-day cutoff most accurately predicts subsequent prognosis than the traditional cutoffs in the post-ICI era.