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用于住院肺癌患者早期分子评估和治疗的一线液体活检

Front-line liquid biopsy for early molecular assessment and treatment of hospitalized lung cancer patients.

作者信息

Parisi Francesca, De Luca Giuseppa, Mosconi Manuela, Lastraioli Sonia, Dellepiane Chiara, Rossi Giovanni, Puglisi Silvia, Bennicelli Elisa, Barletta Giulia, Zullo Lodovica, Santamaria Sara, Mora Marco, Ballestrero Alberto, Montecucco Fabrizio, Bellodi Andrea, Del Mastro Lucia, Lambertini Matteo, Barisione Emanuela, Cittadini Giuseppe, Tagliabue Elena, Spagnolo Francesco, Tagliamento Marco, Coco Simona, Dono Mariella, Genova Carlo

机构信息

Medical Oncology 2 Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Molecular Diagnostic Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

出版信息

Cancer Treat Res Commun. 2024;41:100839. doi: 10.1016/j.ctarc.2024.100839. Epub 2024 Aug 23.

Abstract

BACKGROUND

Molecular characterization is pivotal for managing non-small cell lung cancer (NSCLC), although this process is often time-consuming and patients' conditions might worsen while molecular analyses are processed. Our primary aim was to evaluate the performance of "up-front" next-generation sequencing (NGS) through liquid biopsy (LB) of hospitalized patients with newly detected lung neoplasm in parallel with conventional diagnosis. The secondary aim included longitudinal monitoring through LB of patients with oncogenic alterations at baseline.

METHODS

We enrolled 47 consecutive patients immediately after hospitalization and radiological detection of symptomatic lung neoplasm. LB from peripheral blood was performed at baseline, in parallel with conventional biopsy (CB), when feasible. Additionally, LBs were repeated during treatment in patients with actionable gene alterations at baseline. Oncomine™ Lung cfTNA Research Assay panel was employed for processing plasma samples in NGS.

RESULTS

47 hospitalized patients were enrolled. LB identified 28 patients with gene alterations, including mutations of EGFR (n = 7), KRAS (n = 12), ERBB2 (n = 1), TP53 (n = 2), BRAF (n = 1), one ALK rearrangement, and 4 patients with combined mutations involving EGFR, KRAS and PIK3CA. LB and CB were consistent, except for two patients. Three patients with positive LB for oncogenic drivers did not undergo CB due to contraindications. Median time to molecular results after LB was significantly lower compared to time to molecular report after CB (11 versus 22 days, p < 0.001).

CONCLUSIONS

Despite limited numbers, our study supports the role of front-line LB for improving management of symptomatic patients with lung cancer, potentially leading to early targeted therapy initiation.

摘要

背景

分子特征分析对于非小细胞肺癌(NSCLC)的管理至关重要,尽管这一过程通常耗时较长,且在进行分子分析时患者的病情可能会恶化。我们的主要目的是通过对新发现肺部肿瘤的住院患者进行液体活检(LB)并行常规诊断,来评估“ upfront”二代测序(NGS)的性能。次要目的包括对基线时存在致癌改变的患者通过LB进行纵向监测。

方法

我们连续纳入了47例住院后经影像学检查发现有症状肺部肿瘤的患者。在可行的情况下,于基线时同时进行外周血LB和常规活检(CB)。此外,对基线时存在可操作基因改变的患者在治疗期间重复进行LB。采用Oncomine™ Lung cfTNA Research Assay检测板对NGS中的血浆样本进行处理。

结果

共纳入47例住院患者。LB鉴定出28例基因改变患者,包括EGFR突变(n = 7)、KRAS突变(n = 12)、ERBB2突变(n = 1)、TP53突变(n = 2)、BRAF突变(n = 1)、1例ALK重排,以及4例涉及EGFR、KRAS和PIK3CA的复合突变患者。除2例患者外,LB和CB结果一致。3例LB检测致癌驱动因子呈阳性的患者因禁忌证未进行CB。LB后获得分子结果的中位时间显著短于CB后获得分子报告的时间(11天对22天,p < 0.001)。

结论

尽管样本量有限,但我们的研究支持一线LB在改善有症状肺癌患者管理方面的作用,可能会促使早期启动靶向治疗。

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