SCI
27 July 2024
Analysis of Circulating Tumor DNA Predicts Outcomes of Short Course Consolidation Immunotherapy in Unresectable Stage III Non-Small Cell Lung Cancer
(Journal of Thoracic Oncology; IF: 21.0)
Jun S, Shukla NA, Durm G, Hui AB, Cao S, Ganti AK, Jabbour SK, Kunder C, Alizadeh AA, Hanna NH, Diehn M, Analysis of Circulating Tumor DNA Predicts Outcomes of Short Course Consolidation Immunotherapy in Unresectable Stage III Non-Small Cell Lung Cancer, Journal of Thoracic Oncology (2024), doi: https://doi.org/10.1016/j.jtho.2024.06.024
Correspondence to: Maximilian Diehn，Department of Radiation Oncology, Stanford University, Stanford, CA
The current standard of care for patients with inoperable stage III non-small cell lung cancer (NSCLC) includes chemoradiotherapy (CRT) followed by one year of checkpoint inhibitor (CPI) therapy. However, the optimal duration of consolidation CPI remains unknown. Here, we characterized the relationship between circulating tumor DNA (ctDNA) minimal residual disease (MRD) and clinical outcomes of unresectable locally advanced NSCLC patients treated on a phase 2 trial of short course consolidation immunotherapy after CRT, with the goal of testing if ctDNA may be able to identify patients who do not require a full year of treatment.
对于不可手术的III期非小细胞肺癌(NSCLC)患者，目前的标准治疗包括放化疗(CRT)和随后1年的检查点抑制剂(CPI)治疗。然而，CPI的最佳持续时间仍然未知。在本研究中，我们对接受CRT后短程巩固免疫治疗的不可切除局部晚期NSCLC患者进行了一项2期试验，目的是研究ctDNA是否可以识别不需要1整年治疗的患者，并确定了循环肿瘤DNA (ctDNA)微小残留病(MRD)与患者临床结局之间的关系。
Plasma samples for ctDNA analysis were collected from patients on the BTCRC LUN 16-081 trial after completion of CRT, prior to C2D1 of CPI (i.e. 1 month after treatment start), and at the end of up to 6 months of treatment. Tumor-informed ctDNA MRD analysis was performed using CAPP-Seq. Levels of ctDNA at each time point were correlated with clinical outcomes.
用于ctDNA分析的血浆样本来自BTCRC LUN 16-081试验中的患者，在完成 CRT 后、CPI 第 2 周期 （C2D1） 第 1 天之前（即治疗开始后 1 个月）以及长达 6 个月的治疗结束时，从患者那里收集用于 ctDNA 分析的血浆样本。。采用CAPP-Seq进行肿瘤相关ctDNA MRD分析。各时间点的ctDNA水平与临床结局相关。
Detection of ctDNA predicted significantly inferior progression-free survival (PFS) after completion of CRT (24-month 29% vs 65%, P = 0.0048), prior to C2D1 of CPI (24-month 0% vs 72%, P < 0.0001) and at the end of CPI (24-month 15% vs 67%, P = 0.0011). Additionally, patients with decreasing or undetectable ctDNA levels after one cycle of CPI had improved outcomes compared to patients with increasing ctDNA levels (24-month PFS 72% vs 0%, P < 0.0001). Progression of disease occurred within <12 months of starting CPI in all patients with increasing ctDNA levels at C2D1.
ctDNA检测预测CRT完成后的无进展生存期（24个月29% vs 65%，p = 0.0048）、CPI的C2D1之前（24个月 0% vs 72%，p < 0.0001）和CPI结束时（24个月 15% vs 67%，p = 0.0011）。此外，与ctDNA水平升高的患者相比，1个周期CPI后ctDNA水平降低或检测不到的患者的结局有所改善（24个月无进展生存率为72% vs 0%，p <0.0001）。在 C2D1 ctDNA 水平升高的所有患者中，疾病进展发生在开始 CPI 后不到 12 个月内。
Detection of ctDNA before, during, or after 6 months of consolidation CPI is strongly associated with inferior outcomes. Our findings suggest that analysis of ctDNA MRD may enable personalizing the duration of consolidation immunotherapy treatment.
在6个月CPI巩固治疗之前、期间或之后检测到ctDNA与不良结局强相关。我们的研究结果提示，对ctDNA MRD的分析可能使巩固免疫治疗的持续时间实现个体化。
