Pasello Giulia, Pigato Giulia, Scattolin Daniela, Lando Stefania, Potente Sara, Romualdi Chiara, Roma Anna, Resi Maria Vittoria, Frega Stefano, Ferro Alessandra, Maso Alessandro Dal, Bonanno Laura, Guarneri Valentina, Lazzarini Elisabetta, Indraccolo Stefano
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Medical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
J Exp Clin Cancer Res. 2025 Jun 19;44(1):178. doi: 10.1186/s13046-025-03434-3.
Atezolizumab (A) plus carboplatin-etoposide (CE) represents the new first-line treatment in extensive stage (ES)-Small Cell Lung Cancer (SCLC) patients. This study aims at identifying the association of baseline and dynamic changes of cfDNA, Tumor Fraction (TF) and variant allele frequency (VAF) of tumor-related mutations with median (m) overall (OS) and progression free survival (PFS) in SCLC patients treated with ACE.
This is a single-center prospective exploratory study including treatment-naive ES-SCLC patients eligible to first-line ACE. Liquid biopsies were longitudinally collected at baseline (T0), after cycle 1 (T1) and 2 (T2), at disease progression (T3). cfDNA Next Generation Sequencing (NGS) analysis was performed; genomic profiles and TF were inferred from shallow WGS (sWGS).
Thirty-two patients were included; mPFS and mOS were 5.19 and 7.96 months, respectively. Higher T0 cfDNA (HR 1.44, 95% CI 1.17-1.77, p = 0.0006) and VAF (HR 2.6, 95% CI 1.36-4.93, p = 0.0039) were associated with risk of death; higher T0 cfDNA (HR 1.29, 95% CI 1.08-1.54, p = 0.0049), TF (HR 1.97, 95% CI 1.02-3.82, p = 0.044) and VAF (HR 2.32, 95% CI 1.22-4.42, p = 0.01) were predictors of risk of PD. Among the dynamic changes in the biomarkers under investigation, the association of 10-unit increase of VAF T0-T1 and T0-T2 with OS (HR 1.38, 95% CI 1.01-1.88, p = 0.043; HR 1.56, 95% CI 1.21-2.16, p = 0.008) and PFS (HR 1.69, 95% CI 1.18-2.43, p = 0.004; HR 1.81, 95% CI 1.22-2.70, p = 0.003) was estimated.
T0 and dynamic changes of cfDNA, TF and VAF may help physicians to stratify ES-SCLC patients receiving first-line ACE and to anticipate the clinical course of the disease.
阿替利珠单抗（A）联合卡铂-依托泊苷（CE）是广泛期（ES）小细胞肺癌（SCLC）患者新的一线治疗方案。本研究旨在确定接受ACE治疗的SCLC患者中，循环游离DNA（cfDNA）、肿瘤分数（TF）和肿瘤相关突变的变异等位基因频率（VAF）的基线水平及动态变化与中位（m）总生存期（OS）和无进展生存期（PFS）之间的关联。
这是一项单中心前瞻性探索性研究，纳入初治的符合一线ACE治疗条件的ES-SCLC患者。在基线（T0）、第1周期（T1）和第2周期（T2）后、疾病进展时（T3）纵向采集液体活检样本。进行cfDNA二代测序（NGS）分析；从浅层全基因组测序（sWGS）推断基因组图谱和TF。
纳入32例患者；mPFS和mOS分别为5.19个月和7.96个月。较高的T0期cfDNA（风险比[HR] 1.44，95%置信区间[CI] 1.17 - 1.77，p = 0.0006）和VAF（HR 2.6，95% CI 1.36 - 4.93，p = 0.0039）与死亡风险相关；较高的T0期cfDNA（HR 1.29，95% CI 1.08 - 1.54，p = 0.0049）、TF（HR 1.97，95% CI 1.02 - 3.82，p = 0.044）和VAF（HR 2.32，95% CI 1.22 - 4.42，p = 0.01）是疾病进展风险的预测因素。在所研究的生物标志物的动态变化中，估计VAF T0 - T1和T0 - T2增加10个单位与OS（HR 1.38，95% CI 1.01 - 1.88，p = 0.043；HR 1.56，95% CI 1.21 - 2.16，p = 0.008）和PFS（HR 1.69，95% CI 1.18 - 2.43，p = 0.004；HR 1.81，95% CI 1.22 - 2.70，p = 0.003）相关。
T0期以及cfDNA、TF和VAF的动态变化可能有助于医生对接受一线ACE治疗的ES-SCLC患者进行分层，并预测疾病的临床进程。
