Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions

Mayo‐de‐las‐Casas, Clara; Jordana‐Ariza, Núria; Garzón-Ibañez, Mónica; Balada-Bel, Ariadna; Bertrán-Alamillo, Jordi; Viteri-Ramírez, S.; Reguart, Noemı́; Muñoz-Quintana, M. A.; Lianes-Barragan, P.; Camps, Carlos; Jantús, E.; Remon-Massip, J.; Calabuig, Silvia; Aguiar, David; Gil, M.L. Vilardell; Viñolas, Núria; Santos-Rodríguez, A.K.; Majem, Margarita; García‐Peláez, Beatriz; Villatoro, Sergi; Pérez-Rosado, Ana; Monasterio, J.C.; Ovalle, E.; Catalán, María José; Campos, Raquel Munhoz da Silveira; Morales-Espinosa, Daniela; Martínez‐Bueno, Alejandro; González‐Cao, María; González, Xavier; Moya-Horno, Irene; Sosa, Aaron E.; Karachaliou, Niki; Rosell, Rafael; Molina-Vila, Miguel Ángel

doi:10.1093/annonc/mdx288

Cited by 96 publications

(82 citation statements)

References 19 publications

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“…In addition, allelic fractions were below 0.01% in a significant number of positive paired blood samples, and mutations could only be detected because of the highly sensitive Q‐RT‐PCR used in our study. Commercially available kits and NGS panels would have probably missed some of them, due to insufficient sensitivity (Malapelle et al , ; Mayo‐de‐Las‐Casas et al , ). In contrast, the allelic fractions in nonblood fluids, with a median value of 2.8%, are adequate to be detected by these platforms.…”

Section: Discussionmentioning

confidence: 99%

“…To determine the relative amount of mutations (allelic fraction), serial dilutions of positive in negative genomic DNA, corresponding to allelic fractions 1 : 20 to 1 : 20 000, were periodically run. In the PNA‐Q‐PCR assay, the difference between the C t of the mutated allele and the C t ( ∆ C t ) corresponds to a lower EGFR mutated allelic fraction, ∆ C t = a − ( b × log ML), where ML stands for the relative abundance of the mutant allele, or mutation load (Gonzalez‐Cao et al , ; Mayo‐de‐Las‐Casas et al , ). In consequence, we plotted the ∆ C t vs. the logarithm of the allelic fraction in the serial dilutions and used it to calculate the parameters a and b in the linear equation ∆ C t = a − ( b × log ML).…”

Section: Methodsmentioning

confidence: 99%

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Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

et al. 2019

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Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non‐small‐cell lung cancer and melanoma patients. Cell‐free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA‐Q‐PCR or next‐generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty‐three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine–kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

et al. 2019

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“…Liquid biopsies, such as those evaluating circulating tumor DNA or RNA, circulating tumor cells, and exosomes, are potentially useful for the analysis of tumor cell genetics using blood samples in patients with malignancies, and these approaches have been increasingly translated from research to clinical practice . For example, EGFR mutation testing using blood samples in advanced NSCLC patients is feasible and can be utilized in patient selection for targeted therapy in conditions where tissue testing cannot be achieved . In the current study, approximately half of the patients expected the development of non‐invasive approaches, although blood‐based testing is considered to complement tissue biopsy .…”

Section: Discussionmentioning

confidence: 99%

Questionnaire survey on patient awareness of invasive rebiopsy in advanced non‐small cell lung cancer

et al. 2019

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Background Treatment strategies for patients with non‐small cell lung cancer (NSCLC) depend on various factors including physical condition, complications, tumor histology, and molecular profiling. Even if initial chemotherapy is efficacious, almost all patients develop treatment resistance. Invasive rebiopsy from sites of recurrence might provide insight into resistance mechanisms and aid in the selection of suitable sequential antitumor drugs. However, invasive rebiopsy might be challenging because of limited tissue availability and patient burden. Therefore, this study aimed to assess awareness of invasive rebiopsy among non‐small cell lung cancer patients. Methods This prospective questionnaire survey was performed between June 2015 and March 2016 in patients with advanced non‐small cell lung cancer. The survey was carried out at two time points: before starting first‐line chemotherapy (cohort 1), and at the time of disease progression after initial chemotherapy, but before second‐line chemotherapy (cohort 2). Results In this study, 50 and 30 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, 37 (74%) patients agreed to rebiopsy, if disease progression occurred, whereas 18 (60%) patients in cohort 2 agreed to invasive rebiopsy at disease progression. The primary reasons for rebiopsy rejection were poor physical condition and patient burden related to the initial biopsy. Seven patients answered the survey questions during the treatment course, and the acceptance rate was lower among patients who agreed to rebiopsy at disease progression than before treatment. Conclusions Invasive rebiopsy can lead to distress in some patients. To improve the consent rate for tissue rebiopsy, treatment strategies including rebiopsy should be discussed with patients during the early treatment phase.

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“…As the field moves forwards with immune checkpoint inhibitors, it will be paramount to focus on the identification of biomarkers that are predictive of response. At the same time, it will be important to develop new and dynamic ways to monitor response, such as evaluation of cell-free DNA in the plasma (so-called 'liquid biopsies') [165][166][167][168][169][170].…”

Section: J-n Gallant and CM Lovlymentioning

confidence: 99%

Established, emerging and elusive molecular targets in the treatment of lung cancer

Gallant

Lovly

2018

The Journal of Pathology

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Although histological subtype still underlies tumour classification and treatment, the recognition that lung cancer is, largely, a genetic disease has prompted a push to reconfigure cancer taxonomies according to molecular criteria. In this review, we discuss established (e.g. EGFR, ALK, ROS1, and programmed cell death 1/programmed death-ligand 1), emerging (e.g. MET, RET, and NTRK) and elusive (e.g. TP53, KRAS, and MYC) molecular targets in the treatment of lung cancer. We synthesize a large and rapidly growing body of literature regarding the discovery and therapeutic inhibition of these targets in lung cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions

Cited by 96 publications

References 19 publications

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Questionnaire survey on patient awareness of invasive rebiopsy in advanced non‐small cell lung cancer

Established, emerging and elusive molecular targets in the treatment of lung cancer

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