A Noninvasive System for Monitoring Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors with Plasma DNA

Nakamura, Tomomi; Sueoka‐Aragane, Naoko; Iwanaga, Koichi; Sato, Akemi; Komiya, Kazutoshi; Abe, Tomonori; Ureshino, Norio; Hayashi, Shinichiro; Hosomi, Toshiya; Hirai, Mitsuharu; Sueoka, Eisaburo; Kimura, Shinya

doi:10.1097/jto.0b013e31822956e8

Cited by 66 publications

(70 citation statements)

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“…v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations were identified on LBC material from TC with high reproducibility, feasibility, and informative results 42. LBC specimens were also used to determine the physical status of HPV DNA by in situ hybridization (ISH) and HPV genotyping by polymerase chain reaction (PCR) for identifying patients at high risk of cervical carcinoma43 and of epidermal growth factor receptor (EGFR) mutation for lung carcinoma 44. To search for immunoglobulin gene arrangements, using PCR for ML was reported to be possible with LBC specimens 45.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of liquid‐based cytology with fine needle aspiration specimens for cervical lymphadenopathy

Bandoh

Goto

Akahane

et al. 2016

Diagnostic Cytopathology

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BackgroundCervical lymphadenopathy is a symptom that is frequently seen among outpatients, and it is important to differentiate malignant lesions from reactive lymphoid hyperplasia. Fine needle aspiration (FNA) cytology has been widely used for the diagnosis of cervical lymphadenopathy. However, some limitations of the diagnostic accuracy using conventional smear (CS) cytology have been pointed out. The diagnostic value of liquid‐based cytology (LBC) with FNA specimens has not yet been fully proven.MethodsForty‐two patients with cervical lymphadenopathy who underwent FNA with CS cytology from 2007 to 2011 and 123 patients who underwent FNA with LBC utilizing LBCPREP2™ from 2011 to 2015 were studied. Diagnostic values were compared between the CS and the LBC groups.ResultsOf the total 165 patients representing the combined CS and LBC groups, 81 (49.1%) were diagnosed as benign lymph node and 84 (50.9%) were malignant diseases including 37 (22.4%) of metastatic carcinoma except for thyroid carcinoma, 30 (18.2%) of metastatic thyroid carcinoma, and 17 (10.3%) of malignant lymphoma. The overall statistical values including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CS were 75%, 100%, 100%, 78.9%, and 87.1%, respectively, whereas those values for LBC were 91.2%, 100%, 100%, 90.7%, and 95.3%, respectively. The sensitivity of LBC for malignant diseases tended to be higher than that of CS cytology (p = 0.081).ConclusionLBC with FNA specimens from cervical lymphadenopathy is a useful and reliable method for the diagnosis of malignant diseases, especially of metastatic carcinomas, due to its increased sensitivity compared with CS cytology. Diagn. Cytopathol. 2016;44:169–176. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Diagnostic value of liquid‐based cytology with fine needle aspiration specimens for cervical lymphadenopathy

Bandoh

Goto

Akahane

et al. 2016

Diagnostic Cytopathology

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“…Exon 19 deletions and point mutations including L858R and T790M were detected by the wild inhibiting PCR and quenched probe (WIP-QP) system and the MBP-QP system, respectively. These systems were fully automated using i-densy™ IS-5320 (ARKRAY Inc., Kyoto, Japan), as described previously (28,30,32). Briefly, WIP-QP consisted of wild inhibiting PCR (WIP) and quenched probe (QP) systems, as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

“…As the system utilizes peripheral blood, it is possible to examine T790M repeatedly. Our previous retrospective study using the MBP-QP system demonstrated that T790M was detected in 53-56% of patients who acquired resistance to EGFR-TKI (28,29). In addition, a prospective multicenter observational study was then performed to determine whether T790M detection using MBP-QP system with plasma DNA was useful for monitoring acquired resistance to EGFR-TKI, and T790M was reproducibly detected in 40% of patients whose disease became progressive (30).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, non-invasive liquid biopsy using peripheral blood, which it is possible to repeatedly perform, is a preferable method for monitoring biomarkers. Our group previously developed a fully automated T790M monitoring system using circulating plasma DNA, mutation-biased polymerase chain reaction (PCR) and quenched probe (MBP-QP) system (28). As the system utilizes peripheral blood, it is possible to examine T790M repeatedly.…”

Section: Introductionmentioning

confidence: 99%

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Plasma T790M and HGF as potential predictive markers for EGFR-TKI re-challenge

et al. 2017

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Abstract. Re-challenge with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) has been suggested to potentially improve survival in certain populations of patients with advanced lung cancer, but predictive markers for the success of EGFR-TKI re-challenge have not been identified. The present study analyzed 16 re-challenges with EGFR-TKI undertaken in 12 patients with lung adenocarcinoma by investigating T790M and hepatocyte growth factor (HGF) in plasma coupled with clinical characteristics. EGFR mutations in plasma DNA were detected using the wild inhibiting PCR and quenched probe system for exon 19 deletions, and T790M and L858R were detected using the mutation-biased PCR and quenched probe system. HGF levels in the plasma were measured by enzyme-linked immunosorbent assay, and the ratio of HGF levels prior to re-challenge to those prior to the previous EGFR-TKI treatment was calculated. Two re-challenges demonstrated partial response, six remained as stable disease and eight had progressive disease (PD). A total of 4 of the 5 patients with a history of T790M positivity based on plasma DNA levels had PD. A total of 7 of the 8 patients who had ≥1.5-fold elevation of HGF prior to re-challenge with EGFR-TKI suffered PD. Elevation of the HGF ratio to ≥1.5 was significantly associated with poor response to EGFR-TKI re-challenge. Having no history of T790M and an HGF ratio <1.5 was significantly associated with a positive response to EGFR-TKI re-challenge. A combination of T790M detection and HGF quantification using plasma is a potentially useful assay system for predicting the effect of EGFR-TKI re-challenge. Future prospective studies are required to confirm the predictive validity of these markers. IntroductionEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have produced dramatic anti-cancer effects in patients with non-small cell lung cancer (NSCLC) carrying EGFR activating mutations (1-3). The first generation of EGFR-TKIs, including gefitinib and elrotinib, conferred significantly prolonged progression-free survival (PFS) in these patients. The second generation of these drugs, afatinib, brought a remarkable prolongation of overall survival, up to 33 months, in particular in patients with exon 19 deletions (4). In spite of the effectiveness of EGFR-TKIs, patients eventually acquire resistance. Several treatment strategies have been evaluated in clinical trials and practice following the onset of acquired resistance. First, agents targeted at molecules contributing to acquired resistance have been considered. Based on mechanisms including the secondary EGFR mutation, T790M, MET proto-oncogene, receptor tyrosine kinase (MET) amplification, and hepatocyte growth factor (HGF) overexpression, second and third generation EGFR-TKIs and MET inhibitors have been developed (5-9). Afatinib confers a potent anti-cancer effect against lung cancer cells harboring T790M, but a phase 2b/3 randomized trial revealed that the overall response rate and PFS of patients with lung cancer ...

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“…Empfindliche und qualitativ hochwertige Methoden zeigen, dass cfDNA bei Tumorpatienten zu einem gegenüber anderen Diagnostikmodalitäten früheren Nachweis von Rezidiven und Entwicklungen von Therapieresistenz führt [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Die Analyse der ctDNA besitzt damit ein wichtiges Potenzial für die frühere Identifikation von Therapieversagern, wie sie zum Beispiel während der Therapie des metastasierten kolorektalen Karzinoms mit anti-EGFR Antikörpern auftreten.…”

Section: Introductionunclassified

Zirkulierende Nukleinsäuren – ein neues Universum in der laboratoriumsmedizinischen Diagnostik

Neumaier

2016

LaboratoriumsMedizin

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Zusammenfassung: Zirkulierende zell-freie Nukleinsäu-ren (cfNA, meist als cfDNA bezeichnet) werden zunehmend als eine neue Klasse von diagnostischen Markern wahrgenommen. DNA, mRNA und miRNA zirkulieren weniger in "nackter Form", sondern sind verpackt und entgehen so einem schnellen Abbau im peripheren Blut. Abstract: Circulating cell-free nucleic acids (cfNA, mostly referred to as cfDNA) are increasingly being recognized as a promising new substrate for clinical laboratory diagnostics. DNA, mRNA and miRNA are less likely to circulate in the peripheral blood in a "free naked" form, but rather as a packaged form and thus are fairly protected from degradation. Together with the fact that both qualities and quantities of cfNA vary in a number of important human disorders, this may create an entirely new universe for laboratory diagnostics. First applications enter the arena of routine diagnostic health care, e.g. the sensitive and highly specific detection of tumor mutations that will allow for a molecular profiling of tumor relapse or therapy failure (the so-called "liquid biopsy"). Still, many open questions require resolution including their cross validation with established and important routine biomarkers in the health care lab. Furthermore, critical preanalytical questions, analytical validity and precision need to be addressed to secure the quality of the material analyzed and meaningful results, respectively. Last but not least, circulating nucleic acids uncover a whole new biology of signals traveling through our bodies under various conditions of health and disease. It will be of great scientific importance to understand their biochemical and pathobiochemical implications. It is significant for both the development and implementation of this new diagnostic field that clinical chemistry can provide the required expertise in all Unauthenticated Download Date | 5/11/18 12:36 AM

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A Noninvasive System for Monitoring Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors with Plasma DNA

Abstract: The MBP-QP method is simple, sensitive, and-intriguingly-reflective of clinical course, compared with the other three mutation-detection systems. Thus, the MBP-QP method is an ideal noninvasive monitoring system for detecting T790M in plasma samples.

Cited by 66 publications

References 32 publications

Diagnostic value of liquid‐based cytology with fine needle aspiration specimens for cervical lymphadenopathy

Diagnostic value of liquid‐based cytology with fine needle aspiration specimens for cervical lymphadenopathy

Plasma T790M and HGF as potential predictive markers for EGFR-TKI re-challenge

Zirkulierende Nukleinsäuren – ein neues Universum in der laboratoriumsmedizinischen Diagnostik

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