Sputum cell‐free DNA: Valued surrogate sample for the detection of <i>EGFR</i> exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR‐TKIs

Wang, Zheng; Li, Xiaoguang; Zhang, Lin; Xu, Yan; Wang, Mengzhao; Liang, Li; Jiao, Peng; Li, Yuanming; He, Song; Du, Jie; He, Lei; Tang, Min; Sun, Mingjun; Yang, Li; Jiang, Di; Zhu, Guoqiang; Li, Lin; Liu, Dongge

doi:10.1002/cam4.3817

Cited by 11 publications

(32 citation statements)

References 29 publications

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“…As a consequence, in this study, a “positive bronchus sign” was no prerequisite to find ctDNA in the sputum. Our results confirm earlier studies that sputum is a useful specimen for EGFR mutation analysis, 20-23 but also show that ddPCR is able to detect ctDNA in sputum samples, although cytological examinations do not identify cancer cells in the specimens. This finding is an important milestone to support further studies on the use of sputum for other molecular targets in NSCLC and, most likely, even beyond.…”

Section: Discussionsupporting

confidence: 91%

“…They reported that sputum results matched in 46.2% with confirmed EGFR mutations in tumor samples among the 65 included patients. 22 To improve the detection rate of EGFR , Wu et al combined plasma, sputum, and urine samples and used a next-generation-sequencing platform in 50 patients. They reported a combined sensitivity of 91%, with 84% in plasma and 63% in sputum.…”

Section: Introductionmentioning

confidence: 99%

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Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

Hackner

Buder

Hochmair³

et al. 2021

Clin Med Insights Oncol

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Background: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. Methods: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). Results: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. Conclusions: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

Hackner

Buder

Hochmair³

et al. 2021

Clin Med Insights Oncol

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“…In ascites fluid from a cohort of mixed KRAS-positive and wild-type tumours, KRAS mutations were detected in 100% of the KRAS-positive cohort, and in an additional 19% of tumours deemed wild-type by tissue biopsy [ 34 ]. Sputum and saliva, however, though similarly representative of tumour tissue, are less sensitive sources for cfDNA analysis [ 17 , 35 ].…”

Section: Reliable Molecular Profiling Of Diseasementioning

confidence: 99%

“…Improved ctDNA detection rates have been observed in cfDNA from non-blood sources compared to blood [ 29 ], with the exception of saliva [ 35 ] and sputum [ 17 , 38 ]. This has been repeatedly demonstrated in pleural effusions secondary to lung cancer, with an increased sensitivity to EGFR mutations in malignant pleural effusions over plasma, as well as over cell pellets from the effusions [ 31 , 32 , 33 , 36 ].…”

Section: Reliable Molecular Profiling Of Diseasementioning

confidence: 99%

“…Although other body fluids can be arguably more accessible and less invasive to collect than blood, they have not been afforded equal attention, with ctDNA not discovered in urine until 1995 [ 15 ]. ctDNA has since been found in saliva [ 16 ], sputum [ 17 ], semen [ 18 ], faeces [ 19 ], and cerebrospinal fluid (CSF) [ 20 ]. With respective proximity to cancers of the bladder, head and neck, lungs, prostate and testes, gastro-intestinal tract, and central nervous system (CNS), these fluids may have unique advantages ( Figure 2 ) [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Transcending Blood—Opportunities for Alternate Liquid Biopsies in Oncology

Werner

Warton

Ford

2022

Cancers

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Cell-free DNA (cfDNA) is a useful molecular biomarker in oncology research and treatment, but while research into its properties in blood has flourished, there remains much to be discovered about cfDNA in other body fluids. The cfDNA from saliva, sputum, cerebrospinal fluid, urine, faeces, pleural effusions, and ascites has unique advantages over blood, and has potential as an alternative ‘liquid biopsy’ template. This review summarises the state of current knowledge and identifies the gaps in our understanding of non-blood liquid biopsies; where their advantages lie, where caution is needed, where they might fit clinically, and where research should focus in order to accelerate clinical implementation. An emphasis is placed on ascites and pleural effusions, being pathological fluids directly associated with cancer. We conclude that non-blood fluids are viable sources of cfDNA in situations where solid tissue biopsies are inaccessible, or only accessible from dated archived specimens. In addition, we show that due to the abundance of cfDNA in non-blood fluids, they can outperform blood in many circumstances. We demonstrate multiple instances in which DNA from various sources can provide additional information, and thus we advocate for analysing non-blood sources as a complement to blood and/or tissue. Further research into these fluids will highlight opportunities to improve patient outcomes across cancer types.

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Real‐world analysis of the prognostic value of EGFR mutation detection in plasma ctDNA from patients with advanced non‐small cell lung cancer

Long

Liu

et al. 2023

Cancer Medicine

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Background:The plasma sample has emerged as a promising surrogate sample for EGFR mutation detection in advanced non-small cell lung cancer (NSCLC). In clinical practice, whether EGFR variants in baseline plasma ctDNA of advanced NSCLC can predict prognosis in addition to guiding targeted therapy remains to be further explored. Material and Methods:In total, 315 NSCLC patients were retrospectively enrolled. EGFR mutation data from tissue detected by ARMS-PCR and paired plasma samples within 1 month of admission detected by SuperARMS or ARMS-PCR were collected. The correlation between baseline plasma ctDNA EGFR mutation status and survival was compared.Results: EGFR mutation detection rates in tumor samples and plasma samples were 65.1% (205/315) and 43.8% (138/315). Referred to tissue results, the consistent rate of test ctDNA EGFR alteration by SuperARMS was higher than that detected by ARMS (79.5% vs. 69.0%, p = 0.04), either in stage I-IIIA patients (85.7% vs. 50.0%, p = 0.4) or stage IIIB-IV patients (79.1% vs. 69.4%, p = 0.04).Patients' treatment status and pathological subtype were the two factors that affected plasma ctDNA EGFR alteration detection accuracy. The concordance in non-adenocarcinoma patients was obviously higher than that in adenocarcinoma (p = 0.02), and the concordance in treatment naïve patients was significantly higher than that in relapse patients (p = 0.047). In treatment naïve patients, the median PFS (mPFS) in plasma ctDNA EGFR-positive patients was shorter than that in plasma ctDNA EGFR negative patients (7.0 vs. 10.0 months, p = 0.01). In relapsed patients, the mPFS in plasma ctDNA EGFR-positive patients was 9.0 months versus 11.0 months in plasma ctDNA EGFR negative patients (p = 0.1).

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Sputum cell‐free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR‐TKIs

Cited by 11 publications

References 29 publications

Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients

Transcending Blood—Opportunities for Alternate Liquid Biopsies in Oncology

Real‐world analysis of the prognostic value of EGFR mutation detection in plasma ctDNA from patients with advanced non‐small cell lung cancer

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