Uncommon &lt;em&gt;EGFR&lt;/em&gt; mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Syahruddin, Elisna; Wulandari, Laksmi; Muktiati, Nunuk Sri; Rima, Ana; Soeroso, Noni Novisari; Ermayanti, Sabrina; Levi, Michael H.; Hidajat, Heriawaty; Widjajahakim, Grace; Utomo, Ahmad

doi:10.2147/lctt.s154116

Cited by 22 publications

(26 citation statements)

References 47 publications

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“…22 In comparison, Syahruddin et al reported no S768I mutations despite detecting other uncommon EGFR mutations. 23 Interestingly though, the same report suggests a male preponderance for uncommon mutations as was seen in our study (all three patients with the S768I mutation were male). In our study, we have found that 33.3% of the samples exhibited this mutation in isolation, with an absence of any other mutation.…”

Section: Discussionsupporting

confidence: 83%

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC

et al. 2020

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Background: Lung cancer is the cause of a fourth of all cancer-related deaths. About a third of all lung adenocarcinoma tumours harbour mutations on exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene. Detection of these mutations allows for targeted therapies in the form of EGFR Tyrosine kinase inhibitors. Recently, "liquid biopsies" have emerged as an alternative to conventional tissue mutation detection. Aim: In this pilot study, we attempted to optimize EGFR mutation detection from malignant pleural effusions (MPEs) as "liquid biopsies" when tissue biopsies were unavailable. Resulting mutations were then to be mapped on the EGFR gene and explored using cBioPortal, a public cancer genomic database. Methods and results: We first attempted a direct sequencing approach and showed that single nucleotide variants (SNVs) were likely to be missed in MPEs. We then switched to and optimized an EGFR mutant-specific quantitative polymerase chain reaction-based assay. This assay was piloted on n = 10 pleural effusion samples (one non-malignant pleural effusion as a negative control). 5/9 (55.55%) samples harboured EGFR mutations with 2/9 (22.22%) being exon 19 deletions and 3/9 (33.33%) the S768I mutation. The frequency of the S768I SNV in our study was significantly higher than that observed in other studies (0.2%). Utilizing cBioPortal data, we report that patients with S768I have a shorter median survival time (6 months vs 38 months), progression-free survival time (8 months vs 44 months) and lower tumor mutation count compared to patients with other EGFR mutations. Conclusions: The shorter survival of patients with the S768I SNV predicts aggressive disease and poor prognosis as a result of this mutation. Studies in larger cohorts and/or animal models are necessary to confirm these findings.

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Section: Discussionsupporting

confidence: 83%

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC

et al. 2020

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“…Clove cigarettes contain clove that will make smokers suck in more deeply; thus, smokes containing carcinogenic substances eventually enter the peripheral respiratory tract [ 16 ], [ 18 ]. Syahruddin et al, [ 19 ] found that the EGFR mutations rate among Indonesian population reached 57.1% common mutations (exon 19 ins/dels, L858r) and about 29% uncommon mutations (G719X, exon 20 ins, T790M, L861Q).…”

Section: Discussionmentioning

confidence: 99%

Procalcitonin Level in Non-Small Cell Lung Cancer Patients among Indonesian Population

Soeroso¹,

Tanjung²,

Afiani³

et al. 2018

Open Access Maced J Med Sci

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BACKGROUND:Serum Procalcitonin (PCT) is a biomarker that is frequently used to diagnose an infection. In some cases of thoracic malignancy, procalcitonin level appears to increase. However, the role of procalcitonin to diagnose malignancy is not certain yet, and the causes have not been known.AIM:This study aimed to investigate procalcitonin levels in non-small cell lung cancer patients.METHODS:This was an observational study with a cross-sectional design. All lung cancer patients did not diagnose based on cytology/histopathology results with no evidence nor were signs and symptoms of infection recruited through consecutive sampling. The subtypes of lung cancer include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, staged III and IV. The procalcitonin levels were analysed from blood using immunofluorescent assay. Data were then analysed with the Chi-Square test by Epi Info™ 7 programs in which p-value < 0.05 was considered statistically significant.RESULTS:A total of 68 lung cancer patients fulfilled the criteria of this study, 55 men (80.9%) and 13 women (19.1%). The highest percentage of cytology/histopathology type found was adenocarcinoma (80.9%), and 60.3% of those were diagnosed in stage IV. An increased procalcitonin level (greater than 0.01 ng/mL) occurred in 80.9% of Non-Small Cell Lung Cancer (NSCLC) patients. It appears that the higher the stage of lung cancer, the lower procalcitonin levels would be, although it was not statistically significant. There was no association between lung cancer subtype with procalcitonin levels.CONCLUSION:An increased level of procalcitonin may be an indication not only for infection but also for Non-Small Cell Lung Cancer.

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“…On the basis of preclinical trials some of these uncommon mutations are considered to be partially sensitive to first generation TKI, while others are referred to as resistant to the first and second generation TKI. The frequency of these uncommon EGFR mutations (both TKI sensitive and resistant) has been reported around 1%–10%, although frequency of compound mutations could be as high as 30% of the total EGFR mutated patients 6. In Indian population, the incidence of exon 18 and 20 mutations has been reported as 7% and 3%, respectively, in a cohort of 210 EGFR mutated patients with only two patients harboring mutation in exon 20 along with exon 21 2…”

Section: Introductionmentioning

confidence: 99%

<p>Outcome of uncommon EGFR mutation positive newly diagnosed advanced non-small cell lung cancer patients: a single center retrospective analysis</p>

Kate

Chougule

Joshi

et al. 2019

LCTT

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BackgroundThe significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients.Patients and methodsWe retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan–Meier method and compared between groups using log-rank test.ResultsOut of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8–8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4–28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1–21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2–37.0, P=0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2–41.2, P=0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations.ConclusionUncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.

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Uncommon <em>EGFR</em> mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Cited by 22 publications

References 47 publications

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC

Procalcitonin Level in Non-Small Cell Lung Cancer Patients among Indonesian Population

<p>Outcome of uncommon EGFR mutation positive newly diagnosed advanced non-small cell lung cancer patients: a single center retrospective analysis</p>

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