组织和血浆联合新一代测序在晚期，Treatment-Naïve NSCLC患者中的临床应用

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2024-12-16 DOI:10.1016/j.jtocrr.2024.100778

Helena Bote-de Cabo MD , Marco Siringo MD , Esther Conde MD, PhD , Susana Hernández PhD , Fernando López-Ríos MD, PhD , Alicia Castelo-Loureiro MD , Esther García-Lorenzo MD , Javier Baena MD-PhD , Mercedes Herrera MD , Ana Belén Enguita MD , Yolanda Ruano PhD , Jon Zugazagoitia MD, PhD , Luis Paz-Ares MD, PhD

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引用次数: 0

摘要

基于组织和血浆的下一代测序（NGS）在晚期NSCLC患者中具有互补作用。然而，两种方法联合治疗naïve患者是否有任何额外的临床价值尚不清楚。方法回顾性收集275例treatment-naïve晚期NSCLC患者的临床和基因组数据，这些患者在诊断时接受了基于血浆的NGS。我们分析了两个独立队列的患者数据，每个队列使用不同的基于血浆的NGS方法进行评估：队列1 （n = 127, Guardant360）和队列2 （n = 148, FoundationACT/FoundationOne Liquid CDx）。队列1中的95名患者（75%）和队列2中的108名患者（73%）同时进行了基于扩增子的组织NGS局部检测。结果1组43例患者（34%）和2组49例患者（33%）存在欧洲肿瘤医学学会分子靶标临床可行动性量表（ESCAT） I或II型靶标驱动改变。添加正交活检（组织对液体，或液体对组织）对已经通过一种方法检测到ESCAT I或II靶向驱动因素的病例没有相关的临床价值。相比之下，增加正交活检增加了ESCAT I或II靶标驱动因素的检测，不仅在没有信息检测的病例中（无法检测到循环肿瘤DNA，无法获得/不充分的组织），而且在大约5%的看似有信息但未检测到驱动因素的分子结果的患者中也是如此。在腺癌、吸烟史不超过20包年和腹部转移的患者中，血浆中ESCAT I或II靶向驱动因子的患病率明显更高。我们的研究表明，当初始方法未检测到ESCAT I或II靶标驱动因子时，应考虑增加顺序正交活检，包括看似信息丰富的分子分析病例。

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Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC

Introduction

Tissue and plasma-based next-generation sequencing (NGS) have complementary roles in patients with advanced NSCLC. Nevertheless, whether there is any added clinical value in combining both methods in the treatment of naïve patients remains unclear.

Methods

We retrospectively collected clinical and genomic data from 275 patients with treatment-naïve advanced NSCLC who had undergone plasma-based NGS at diagnosis in our institution. We analyzed patient data in two separate cohorts, each assessed with a different plasma-based NGS method: cohort 1 (n = 127, Guardant360), and cohort 2 (n = 148, FoundationACT/FoundationOne Liquid CDx). Ninety-five patients (75%) in cohort 1 and 108 patients (73%) in cohort 2 underwent concurrent amplicon-based tissue NGS testing locally.

Results

Forty-three patients in cohort 1 (34%) and 49 patients in cohort 2 (33%) harbored European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) I or II targetable driver alterations. The addition of orthogonal biopsy (tissue to liquid, or liquid to tissue) offered no relevant clinical value in cases with ESCAT I or II targetable drivers already detected by one method. In contrast, adding orthogonal biopsy incremented the detection of ESCAT I or II targetable drivers not only in cases with uninformative testing (undetectable circulating tumor DNA, unavailable/inadequate tissue) but also in about 5% of the patients with seemingly informative but driver undetected molecular results. The prevalence of ESCAT I or II targetable drivers in plasma was significantly higher in patients with adenocarcinoma, 20 pack-year or less smoking history, and abdominal metastases.

Conclusions

Our study suggests that the addition of sequential orthogonal biopsy should be considered whenever an ESCAT I or II targetable driver has not been detected by the initial method, including cases with seemingly informative molecular analysis.

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