Quantification of plasma EGFR mutations in patients with lung cancers: Comparison of the performance of ARMS-Plus and droplet digital PCR

Wang, Lin; Guo, Qiaojuan; Yu, Wenjing; Qiao, Lihua; Zhao, Mingna; Zhang, Chenzi; Hu, Xiaomeng; Yang, Guohua; Xiong, Liwen; Lou, Jiatao

doi:10.1016/j.lungcan.2017.10.007

Cited by 20 publications

(18 citation statements)

References 18 publications

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“…Therefore, we plan to combine plasma, sputum, and urine to further explore the concordance and relationship between these liquid samples and tumor tissues. The detection method is another issue needed to be considered carefully since sensitivities of different methods are diverse . NGS, as a sensitive method, can discover a tremendous number of driver gene variations involving therapeutic target genes and acquired drug‐resistant genes simultaneously and has been increasingly applied to clinical practice recently .…”

Section: Introductionmentioning

confidence: 99%

Differences in the genomic profiles of cell‐free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC

Yang

et al. 2019

Cancer Medicine

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Liquid biopsy has provided an efficient way for detection of gene alterations in advanced non‐small‐cell lung cancer (NSCLC). However, the correlation between systematic determination of somatic genomic alterations in liquid biopsy and tumor biopsy still remained unclear, and the concordance rate between cell‐free DNA (cfDNA) and matched tumor tissue DNA needs to be increased. A prospective study was performed to detect differences in genetic profiles of cfDNA in sputum, plasma, urine, and tumor tissue from 50 advanced NSCLC patients in parallel by the same next‐generation sequencing (NGS) platform. Driver genes alterations were identified in cfDNA sample and matched tumor sample, with an overall concordance rate of 86% in plasma cfDNA, 74% in sputum cfDNA, 70% in urine cfDNA, and 90% in cfDNA of combination of plasma, sputum, and urine. And the concordant rate of cfDNA in sputum in patients with smoking history was higher than that in patients without history of smoking (89% vs. 66%, P = 0.033) and equal to that in plasma cfDNA of the smoking patients (89% vs. 89%). In conclusion, sputum cfDNA can be considered as an alternative medium to liquid biopsy, while the complementarity of genomic profiles in cfDNA among plasma, sputum, and urine was beneficial to detect more diver genes alterations and improve the utility of liquid biopsy in advanced NSCLC (Liquid Biopsy for Detection of Driver Mutation in NSCLC; NCT02778854).

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Section: Introductionmentioning

confidence: 99%

Differences in the genomic profiles of cell‐free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC

Yang

et al. 2019

Cancer Medicine

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“…For these reasons, researchers have developed a number of liquid biopsy platforms that can be utilized as complements to or in lieu of tissue biopsy . With the advancement of genotyping assays—namely, droplet digital polymerase chain reactions (ddPCRs) and beads, emulsions, amplification, and magnetics (BEAMing) digital polymerase chain reaction (dPCR)—the mutation status of a patient can be detected using cell‐free plasma DNA . However, studies on the efficacy of osimertinib using plasma testing remain scarce and limited in terms of patient numbers .…”

Section: Introductionmentioning

confidence: 99%

Real‐world outcomes of NSCLC patients receiving tissue or circulating tumor DNA‐guided osimertinib treatment

Yang

Chen

et al. 2019

Cancer Medicine

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Background Osimertinib yields significant tumor responses and durations of progression‐free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy‐guided treatment is still limited. This study examined the real‐world benefits of osimertinib in patients with tissue or plasma T790M mutations. Methods From January 2016 to June 2018, a total of 183 non‐small‐cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials. Results T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2‐NR) in all the T790M‐positive patients and 10.1 months (interquartile range: 5.9‐NR) in the plasma T790M‐positive patients. The overall survival, meanwhile, was not reached, whereas the one‐year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M‐positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M‐positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS. Conclusions In this retrospective real‐world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials.

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“…The reasons for false positives can be divided into detection causes and non-detection causes. Detection causes mainly include: (i) Determination of cut-off values for EGFR mutations that were defined too low, (ii) Single tissue biopsy specimens were difficult to reflect the genetic characteristics of the whole tumor on intratumor heterogeneity, which meant even the result of cfDNA may be correct sometimes, false positive results by tissue biopsy conduced an opposite conclusion, (iii) Non-specific annealing of PCR primers could result in a false positive when the concentration of wild-type template was much higher than mutant template (20). Furthermore, the time interval between tissue samples acquired first and plasma samples acquired later may also cause false positives due to the tumor burdens becoming more severe as the disease progressed.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, 25 full-text articles were identified and reviewed. Of the included articles, 14 studied ddPCR (10,11,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) and 16 studied ARMS-PCR (10, 11, 13-15, 20, 22, 27-35). Specifically, five articles made direct comparisons between ddPCR and ARMS-PCR (10,11,15,20,22).…”

Section: Study Selection and Quality Assessmentmentioning

confidence: 99%

Diagnostic Accuracy of Droplet Digital PCR and Amplification Refractory Mutation System PCR for Detecting EGFR Mutation in Cell-Free DNA of Lung Cancer: A Meta-Analysis

Liang

et al. 2020

Front. Oncol.

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Background: Epidermal growth factor receptor (EGFR) mutation testing in plasma cell-free DNA (cfDNA) from advanced lung cancer patients is an emerging clinical tool. This meta-analysis was designed to determine the diagnostic accuracy of two common PCR systems, droplet digital PCR (ddPCR) and amplification refractory mutation system PCR (ARMS-PCR), for detecting EGFR mutation in cfDNA. Materials and methods: A systematic search was carried out based on PubMed, Web of science, Embase and the Cochrane library. Data from eligible studies were extracted and pooled to calculate the sensitivity, specificity, diagnostic odds ratio (DOR), area under the summary receiver-operating characteristic curve (AUROC), using tissue biopsy results as the standard method. Subgroup analyses were performed regarding EGFR mutation type, tumor stage, and EGFR-TKI treatment. Results: Twenty-five studies involving 4,881 cases were included. The plasma testing sensitivity, specificity, DOR, and AUROC, compared with the matched tumor tissues, were 72.1%, 95.6%, 38.5, 0.89 for ddPCR, and 65.3%, 98.2%, 52.8, 0.71 for ARMS-PCR, respectively, through indirect comparison, significant differences were found in sensitivity (P = 0.003) and specificity (P = 0.007). Furthermore, significant difference was found in sensitivity between tumor stage subgroups (IIIB-IV subgroup vs. IA-IV subgroup) in ARMS-PCR (73.7 vs. 64.2%, P = 0.008), but not in ddPCR (72.5 vs. 71.2%, P = 0.756). Conclusions: This study demonstrates that ddPCR and ARMS-PCR have a high specificity with a practical sensitivity for detecting EGFR mutation in cfDNA, which supports their application as a supplement or a conditional-alternative to tissue biopsy in clinical practice for genotyping. It seems that ddPCR has a higher sensitivity than ARMS-PCR, especially in early stages.

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Quantification of plasma EGFR mutations in patients with lung cancers: Comparison of the performance of ARMS-Plus and droplet digital PCR

Cited by 20 publications

References 18 publications

Differences in the genomic profiles of cell‐free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC

Differences in the genomic profiles of cell‐free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC

Real‐world outcomes of NSCLC patients receiving tissue or circulating tumor DNA‐guided osimertinib treatment

Diagnostic Accuracy of Droplet Digital PCR and Amplification Refractory Mutation System PCR for Detecting EGFR Mutation in Cell-Free DNA of Lung Cancer: A Meta-Analysis

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