Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients

Yang, Weixiong; You, Na; Jia, Minghan; Yeung, Sai Ching Jim; Ou, Wei; Yu, Ming; Wang, Yinguang; Fu, Xiangkai; Zhang, Zhanfei; Yang, Jiali; Lao, Zhengqi; Liu, Zhenguo; Zeng, Bo; Ou, Qiuxiang; Wu, Xue; Shao, Yang; Hong, Xiaoyu; Wang, Siyu; Cheng, Chao

doi:10.1016/j.lungcan.2020.06.009

Cited by 15 publications

(22 citation statements)

References 21 publications

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“…Copy number variations (CNVs) were detected using ADTEx (http://adtex. sourceforge.net) with default parameters as reported by previous studies (14)(15)(16). To eliminate sequencing artifact, a local bioinformatics pipeline was performed.…”

Section: Data Processingmentioning

confidence: 99%

Dynamic cfDNA Analysis by NGS in EGFR T790M-Positive Advanced NSCLC Patients Failed to the First-Generation EGFR-TKIs

Wang

et al. 2021

Front. Oncol.

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PurposeCirculating cell-free DNA (cfDNA) level has been demonstrated to be associated with efficacy in first generation EGFR TKIs in non-small cell lung cancer (NSCLC). However, the role of dynamic cfDNA analysis using next-generation sequencing (NGS) in patients with subsequent third-generation EGFR TKIs remains unclear.MethodsFrom 2016 to 2019, 81 NSCLC patients with EGFR T790M mutation either in tissue or plasma who received third-generation EGFR TKIs treatment were enrolled. CfDNA were sequenced by NGS with a 425-gene panel. The association of clinical characteristics, pretreatment, dynamic cfDNA and T790M level with outcomes in patients treated with the third-generation TKIs were analyzed.ResultsIn univariate analysis, the median PFS of patients with undetectable cfDNA level during treatment was significantly longer than those with detectable cfDNA (16.97 vs. 6.10 months; HR 0.2109; P < 0.0001). The median PFS of patients with undetectable T790M level during treatment was significantly longer than those with detectable T790M (14.1 vs. 4.4 months; HR 0.2192; P < 0.001). Cox hazard proportion model showed that cfDNA clearance was an independent predictor for longer PFS (HR 0.3085; P < 0.001) and longer OS (HR 0.499; P = 0.034). The most common resistant mutations of the third-generation TKIs were EGFR C797S (24%). CDK6 CNV, GRIN2A, BRCA2, EGFR D761N, EGFR Q791H, EGFR V843I, and ERBB4 mutation genes may possibly be new resistant mechanisms.ConclusionsPatients with undetectable cfDNA during the third-generation EGFR TKI treatment have superior clinical outcomes, and dynamic cfDNA analysis by NGS is valuable to explore potential resistant mechanisms.

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Section: Data Processingmentioning

confidence: 99%

Dynamic cfDNA Analysis by NGS in EGFR T790M-Positive Advanced NSCLC Patients Failed to the First-Generation EGFR-TKIs

Wang

et al. 2021

Front. Oncol.

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“…All DNA was quantified using the dsDNA HS Assay Kit on a Qubit Fluorometer (Life Technologies, Waltham, MA, USA). Sequencing libraries were prepared using the KAPA Hyper Prep Kit (KAPA Biosystems, Roche, Basel, Switzerland), as described previously [10][11][12]. Indexed DNA libraries were pooled for probe-based hybridization capture of the targeted gene regions covering over 400 cancer-related genes for all solid tumors, all of which contain all exons of ROS1 and select introns for the detection of ROS1 fusions.…”

Section: Dna Extraction and Targeted Enrichmentmentioning

confidence: 99%

Molecular and clinicopathological characteristics of ROS1‐rearranged non‐small‐cell lung cancers identified by next‐generation sequencing

et al. 2020

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ROS1 gene rearrangements have been reported in diverse cancer types including non-small-cell lung cancer (NSCLC), and with a notably higher prevalence in lung adenocarcinoma. The tyrosine kinase inhibitors, crizotinib, lorlatinib, and entrectinib, have demonstrated favorable efficacy in treating ROS1-rearranged NSCLCs. Herein, we retrospectively reviewed 17 158 NSCLC patients whose tumor specimen and/or circulating cell-free DNA underwent comprehensive genomic profiling. A total of 258 unique patients were identified with ROS1 rearrangements, representing an overall prevalence of approximately 1.5% of ROS1 fusions in newly diagnosed and relapsed NSCLC patients. CD74 (38%) was the most common fusion partner of ROS1, followed by EZR (13%), SDC4 (13%), SLC34A2 (10%), and other recurrent fusion partners with lower frequencies, including TPM3, MYH9, and CCDC6. Variant breakpoints occurred in ROS1 introns 33 (37%), 31 (25%), 32 (17%), and 34 (11%) with no obvious hotspots. CD74 (63%) and EZR (50%) were more frequently fused to ROS1 intron 33 than other introns, while ROS1 intron 31 was most frequently fused with SDC4 (79%) and SLC34A2 (81%). Crizotinib progression-free survival (PFS) was not significantly different between fusion variants involving breakpoints in different ROS1 introns, nor was there a significant difference in PFS between CD74-ROS1 and non-CD74-ROS1 groups of patients. Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS. ROS1 mutations, including G2032R, were observed in approximately 33% of post-crizotinib samples. Collectively, we report the prevalence of ROS1 fusions in a large-scale NSCLC population and the efficacy of crizotinib in treating patients with ROS1-rearranged NSCLC.

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“…Somatic mutations were detected with VarScan2. Copy number variations (CNVs) were detected using ADTEx (http://adtex.sourceforge.net) with default parameters as reported by previous studies 21–23 . To eliminate sequencing artifact, a local bioinformatics pipeline was performed.…”

Section: Methodsmentioning

confidence: 99%

“…Copy number variations (CNVs) were detected using ADTEx (http://adtex.sourceforge.net) with default parameters as reported by previous studies. [21][22][23] To eliminate sequencing artifact, a local bioinformatics pipeline was performed. First, we used a local WBCs database, containing recurrent somatic alterations from WBCs of 400 patients, to eliminate the sequencing artifacts.…”

Section: Data Processingmentioning

confidence: 99%

Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies

Zhang

Chen

Chong

et al. 2020

Clinical & Translational Med

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• Plasma ctDNA-based diagnosis was more sensitive than conventional computed tomography scanning in 40% of patients, gaining time for clinical management. • Plasma tumor mutation burden was a potential marker to predict the therapeutic outcomes of human epidermal growth factor receptor 2 (HER2)targeted therapy in GC. • HER2-positive patients with high TMB might gain more therapeutic benefits from immunotherapy instead of HER2-targeted regimens that required further studies and validations.

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Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients

Cited by 15 publications

References 21 publications

Dynamic cfDNA Analysis by NGS in EGFR T790M-Positive Advanced NSCLC Patients Failed to the First-Generation EGFR-TKIs

Dynamic cfDNA Analysis by NGS in EGFR T790M-Positive Advanced NSCLC Patients Failed to the First-Generation EGFR-TKIs

Molecular and clinicopathological characteristics of ROS1‐rearranged non‐small‐cell lung cancers identified by next‐generation sequencing

Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies

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