Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non–Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR

Watanabe, Masaru; Kawaguchi, Tomoya; Isa, Shun‐ichi; Ando, Masahiko; Tamiya, Akihiro; Kubo, Akihito; Sasaki, Hideo; Takeo, Sadanori; Adachi, Hirofumi; Tagawa, Tetsuzo; Kakegawa, Seiichi; Yamashita, Motohiro; Kataoka, Kazuhiko; Ichinose, Yukito; Takeuchi, Yukiyasu; Sakamoto, Kazuhiro; Matsumura, Akira; Koh, Yasuhiro

doi:10.1158/1078-0432.ccr-14-2151

Cited by 201 publications

(182 citation statements)

References 40 publications

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“…In the present study, we detected T790M mutation in 29.4% of the pretreatment specimens with EGFR mutations (45 of 153 cases) using a CAST-PCR, and in 40% of pretreatment specimens with EGFR mutations (8 of 20cases) using a digital PCR. In contrast to our study, Watanabe et al (12) and Iwama et al (14) reported that they detected T790M mutations in 79.9% (298 of 373 cases) and 100% (25 of 25 cases) of pretreatment FFPE tissue specimens, respectively, using a digital PCR. Moreover, the incidence of pretreatment T790M mutations in the present study was lower in comparison to previous studies.…”

Section: Discussioncontrasting

confidence: 99%

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The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR

Tatematsu¹,

Okuda²,

Suzuki³

et al. 2017

J. Thorac. Dis.

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Background: A gatekeeper T790M mutation is thought to cause resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The detection of a 2nd mutation is important for planning the next therapy when patients acquire resistance to the first line EGFR-TKI. Conclusions: Our study shows that the pretreatment incidence of T790M mutation was less than that reported in previous studies. In order to clinically use pretreatment EGFR T790M mutation identification method, we should clarify the adequate methods and tissue preserved status.

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Section: Discussioncontrasting

confidence: 99%

“…However, it has been reported that a small quantity of T790M mutation would be included in the pretreatment tumor of EGFR-TKIs (12)(13)(14). Watanabe et al (12) reported that pretreatment EGFR T790M mutations were detected in NSCLC patients with…”

Section: Introductionmentioning

confidence: 99%

The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR

Tatematsu¹,

Okuda²,

Suzuki³

et al. 2017

J. Thorac. Dis.

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“…The most common known mechanism is the acquisition of T790M that renders the kinase resistant to the first-line TKI (27,28). Studies showed that T790M existed at a low frequency within the tumor cells pretreatment and became the dominant clone after selection pressure of EGFR-TKI therapy (29). In addition, preclinical studies also demonstrated that a second mutation of T790M could be successfully induced in PC-9 lung cancer cells after about 120 days culture with TKI (30).…”

Section: Early Intervention Of Radiotherapy In Tki Therapymentioning

confidence: 99%

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

Xia

Zhang

2017

J. Thorac. Dis.

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In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) was greatly promoted by the discovery of oncogenic drivers and the development of targeted therapies specific for these drivers. Somatic mutations in epidermal growth factor receptor (EGFR) are the most common type in patients with NSCLC. Small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR produced relatively high response rate and long duration with acceptable toxicity profile. Also, the life expectancy in patients with active EGFR mutation has been significantly prolonged than the past. Additionally, evolution of advanced imaging and radiation techniques has expanded the indications for radiotherapy in complex clinical situation. All of those factors contributed to the widely use of radiotherapy for advanced NSCLC treated with TKI therapy. In this review, we will discuss how to integrate radiotherapy into the comprehensive treatment of patients with TKI therapy in order to maximize the therapeutics effect.

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“…Numerous cutting-edge platforms have been developed (12,13), and droplet digital polymerase chain reaction (ddPCR) is one of the most accurate and robust methods for absolute nucleic acid quantification (13). Previous studies using these platforms have demonstrated a sensitivity and specificity >90% for detecting EGFR mutations in cfDNA (14)(15)(16)(17). Notably, early detection of T790M mutation up to 16 weeks prior to radiographic progression was shown in a proof-of-concept study that collected a fraction of representative plasma samples in each patient (15).…”

Section: Introductionmentioning

confidence: 99%

Dynamic monitoring of EGFR mutations in circulating cell-free DNA for EGFR-mutant metastatic patients with lung cancer: Early detection of drug resistance and prognostic significance

Weng

Liu

et al. 2017

Oncology Letters

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Abstract. Detecting genetic mutations in circulating cell-free DNA (cfDNA) is a promising approach of liquid biopsy. Between June 2014 and May 2015, 168 plasma samples were collected monthly from 20 patients with metastatic lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation receiving gefitinib therapy. Clinically relevant EGFR mutations, including exon 19 deletion, L858R and T790M, were quantified using droplet digital polymerase chain reaction. In baseline samples, 19 (95.0%) patients had the same mutation with the matched tumors, and pretreatment T790M mutations were also detected in 3 (15.0%) patients. The dynamics of EGFR mutations were generally associated with treatment response for patients with or without measurable disease. For patients with immeasurable tumor deposits, monitoring disease evolution using cfDNA-based mutation quantification appeared to be more reliable compared with measuring the diameters of target tumor lesions. In addition, molecular progressive disease, defined as a ≥20% increase of EGFR mutation concentration compared with the lowest concentration recorded during treatment, was tracked up to 8 months prior to objective progression. In survival analysis, sex (P= 0.005), pretreatment T790M mutation status (P= 0.006), T790M mutation status at the disease progression (P= 0.043) and growth rate of EGFR mutations (P= 0.023), had a significant impact on median progression-free survival. In conclusion, dynamic monitoring of EGFR mutations in cfDNA is feasible and appears to be useful in early prediction of drug resistance for patients with lung cancer receiving EGFR tyrosine kinase inhibitors.

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Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non–Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR

Cited by 201 publications

References 40 publications

The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR

The detectability of the pretreatment EGFR T790M mutations in lung adenocarcinoma using CAST-PCR and digital PCR

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

Dynamic monitoring of EGFR mutations in circulating cell-free DNA for EGFR-mutant metastatic patients with lung cancer: Early detection of drug resistance and prognostic significance

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