Sample Features Associated with Success Rates in Population-Based EGFR Mutation Testing

Shiau, Carolyn J; Babwah, Jesse Paul; Santos, Gilda da Cunha; Sykes, Jenna; Boerner, Scott; Geddie, William R.; Leighl, Natasha B.; Wei, Chun; Kamel‐Reid, Suzanne; Hwang, David; Tsao, Ming‐Sound

doi:10.1097/jto.0000000000000196

Cited by 71 publications

(109 citation statements)

References 45 publications

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“…As previously established, the rate of EGFR mutations is markedly higher in Asians compared with other ethnic groups such as Caucasian (49,50). Consequently, we suggested that VeriStrat classification might be more useful to identify patients with primary or secondary resistance to EGFR-TKIs, while the classification model in the present study may focus on EGFR-TKI-sensitive populations.…”

Section: Discussionmentioning

confidence: 64%

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Tang

Wang

et al. 2018

Oncol Lett

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Abstract. Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. IntroductionLung cancer remains a common cause of mortalities worldwide, accounting for 1.6 million mortalities in 2012 and ~20% of all cancer mortalities (1). Non-small cell lung cancer (NSCLC) is the predominant type of the disease with ~80% of cases (1). In the last decade, the important discovery of mutations in the epidermal growth factor receptor (EGFR) gene had led to the development of targeted therapy and personalized medicine (2). One class of anti-tumor drugs that target EGFR is a group of small molecule inhibitors that inhibit the tyrosine kinase domain of EGFR, EGFR-tyrosine kinase inhibitors (TKIs). Examples of EGFR-TKIs include gefitinib and erlotinib (3,4).EGFR-TKIs have demonstrated initial success in some patients with activating mutations (5). However, numerous patients do not respond to the drug (6-8). Therefore, the identification of biomarkers that are predicative of response to the drug became a key issue for doctors to select the optimal therapy. To date, mutations in the EGFR gene (exon 19 deletion, exon 18 G719X and exon 21 L858R) have been reported to be predictors ...

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Section: Discussionmentioning

confidence: 64%

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Tang

Wang

et al. 2018

Oncol Lett

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“…Archival tissue serves as excellent material for further tumour testing, and such samples are currently used for almost all predictive and prognostic biomarker testing across tumour sites 42 .…”

Section: Molecular Testing: Pathology Perspectivesmentioning

confidence: 99%

Management of Egfr-Mutated Non-Small-Cell Lung Cancer: Practical Implications from a Clinical and Pathology Perspective

Cabanero

Sangha²,

Sheffield

et al. 2017

Current Oncology

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Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy.In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed.

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“…Specimens with high tumour cellularity, even if they are small, are preferred for molecular testing over those with low tumour cellularity 45,47 . Whenever possible, the entire block and unused precut slides, rather than recut slides, should be sent for molecular testing.…”

Section: Pathology Perspectivesmentioning

confidence: 99%

“…In addition to determining malignancy, lung origin, and pathologic subtype, pathologists evaluate diagnostic specimens to ensure that samples meet the criteria for molecular analysis. Whether cytology or biopsy specimens are obtained, tumour cellularity is the key determinant of the likelihood of successful molecular testing [45][46][47][48] ; both techniques can potentially yield adequate material for diagnostic molecular tests 49 . With respect to cytology specimens, preparation of a cell block is still preferred 24,50 , but other specimens are also suitable for analysis 27 .…”

Section: Pathology Perspectivesmentioning

confidence: 99%

Improving Molecular Testing and Personalized Medicine in Non-Small-Cell Lung Cancer in Ontario

et al. 2017

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Sample Features Associated with Success Rates in Population-Based EGFR Mutation Testing

Cited by 71 publications

References 45 publications

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Management of Egfr-Mutated Non-Small-Cell Lung Cancer: Practical Implications from a Clinical and Pathology Perspective

Improving Molecular Testing and Personalized Medicine in Non-Small-Cell Lung Cancer in Ontario

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