Impact of Cytological Sampling on EGFR Mutation Testing in Stage III-IV Lung Adenocarcinoma

Davies, Rhian Siân; Smith, C.; Edwards, Gwenllian; Butler, Rachel; Parry, D. H.; Lester, J.F.

doi:10.1155/2017/9614938

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…Liu et al showed a sensitivity of 81.8% and specificity of 80% for EGFR mutation detection in effusion sample with tissue biopsy sample [12]. Davies et al had successful EGFR mutation analysis in nine of 10 (90%) cases with malignant pleural effusion [14]. Liu et al studied 192 paired malignant effusion and biopsy and found a higher mutation rate in biopsy of 62% compared to effusion of 58.9%.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Mutation Frequency in Squamous Cell Carcinoma and Its Diagnostic Performance in Cytological Samples: A Molecular and Immunohistochemical Study

et al. 2019

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Background Epidermal growth factor receptor (EGFR) mutation is the most frequent mutation tested in lung cancer for targeted therapy in the era of personalized medicine. Knowledge about EGFR mutation is constantly expanding regarding its frequency, clinicopathological association, advancements in testing methodology and sample requirement. We investigated EGFR mutation frequency in non-small cell lung cancer (NSCLC) in North Indian patients and evaluated its diagnostic performance in cytological samples. Methods Molecular EGFR testing was done in 250 cases of NSCLC by both real-time polymerase chain reaction (PCR) (Therascreen) and mutation-specific EGFR immunohistochemistry (IHC). Thirty cases had both cytology samples and biopsy including 20 pleural effusions and 10 fine-needle aspirates. EGFR mutation concordance between pleural effusion and biopsy was studied. Results EGFR mutation was overall 31.6% in NSCLC with 36.5% in adenocarcinoma and 15% in squamous cell carcinoma. L858R mutation accounted for 50.7% and DEL19 for 39.3% of total EGFR mutations. Complex mutations were seen in 2% of cases. Sensitivity of mutation-specific EGFR IHC was 48.3% and specificity was 92.3%. L858R showed higher sensitivity (55% vs. 33.3%) but similar specificity (93.2% vs. 91.3%) compared to DEL19. EGFR mutation was successful in 95% of pleural effusion and showed 83.3% concordance with tissue biopsy. Conclusions EGFR mutation frequency in North Indian patients was comparable to that of Asia-Pacific region and showed a similar pattern of histological distribution. EGFR mutation in squamous cell carcinomas is increasingly recognized which was 15% in our study. Mutation-specific EGFR IHC shows variable but generally low sensitivity and considering its significant pre- and post-analytical variables, it should be highly discouraged in patient management. Cytological samples may not only serve as suitable alternative but may be complementary to tissue biopsies.

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Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Mutation Frequency in Squamous Cell Carcinoma and Its Diagnostic Performance in Cytological Samples: A Molecular and Immunohistochemical Study

et al. 2019

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“…Initial tumor testing for EGFR or other mutations is routinely undertaken using direct biopsy of the tumor 10 , 11 ; however, around 30% of NSCLC patients may be unable to provide a biopsy sample that is suitable for EGFR mutation analysis at diagnosis or following disease progression. 11 – 13 In addition, tissue biopsies, particularly re-biopsies at the point of progression on initial treatment, are invasive and costly, and therefore not always feasible. 10 , 11 , 14 – 16 Given these drawbacks, the less invasive liquid biopsy may be preferred over traditional tumor biopsy, particularly in monitoring for resistance.…”

Section: Advances In Egfr Mutation Testingmentioning

confidence: 99%

Afatinib for the treatment of EGFR mutation-positive NSCLC: A review of clinical findings

Harvey

Adams

Beardslee

et al. 2020

J Oncol Pharm Pract

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors represent the standard of care in patients with EGFR mutation-positive ( EGFRm+) non-small cell lung cancer (NSCLC). The availability of several EGFR tyrosine kinase inhibitors approved for use in the first-line or later settings in NSCLC warrants an in-depth understanding of the pharmacological properties of, and clinical data supporting, these agents. The second-generation, irreversible ErbB-family blocker, afatinib, has been extensively studied in the context of EGFRm+ NSCLC. Results from the LUX-Lung 3 and 6 studies showed that afatinib was more active and better tolerated than chemotherapy in patients with tumors harboring EGFR mutations. Subanalysis of these trials, along with real-world data, indicates that afatinib is active in patients with certain uncommon EGFR mutations (S768I/G719X/L861Q) as well as common mutations (Del19/L858R), and in patients with active brain metastases. In LUX-Lung 7, a head-to-head phase IIb trial, afatinib improved progression-free survival and time-to-treatment failure versus the first-generation reversible EGFR tyrosine kinase inhibitor, gefitinib, albeit with a higher incidence of serious treatment-related adverse events. Nevertheless, afatinib is generally well tolerated, and adverse events are manageable through supportive care and a well-defined tolerability-guided dose adjustment scheme. In this review, we provide a detailed overview of the pharmacology, efficacy, and safety of afatinib, discuss treatment sequencing strategies following emergence of different resistance mechanisms, and shed light on the economic impact of afatinib. We also provide a comparison of afatinib with the available EGFR tyrosine kinase inhibitors and discuss its position within treatment strategies for patients with EGFRm+ NSCLC.

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“…The role of cytopathology is gaining importance with the increasing use of minimally invasive techniques like endobronchial ultrasound-guided fine-needle aspiration (EBUS FNA) which can frequently provide adequate material for diagnosis, immunohistochemistry, and mutation analysis [51]. In a study conducted by Rhian et al for assessing the impact of cytological sampling on EGFR mutation testing in stage III-IV lung adenocarcinoma, it was found that cytological sampling was almost as effective as histological methods at acquiring adequate samples for analysis [52]. Current recommendations suggest that molecular analysis be conducted on highly sensitive polymerase chain reaction (PCR) based methods and/or FISH on lung cytology.…”

Section: Role Of Lung Cytology In Lung Cancer Diagnosismentioning

confidence: 99%

Molecular Therapeutics of Non-Small Cell Lung Cancer (NSCLC) and Challenges in Repeat Tissue Biopsy

Ganesha¹,

Naik²,

Mufti³

et al. 2021

ALC

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With advances in targeted and personalized treatment for lung cancer, molecular analysis of tumors is routinely performed for sequencing of treatment options in patients with advanced non-small-cell lung cancer (NSCLC). Oncogene addiction due to driver mutations includes EGFR exon 20 insertion mutations, MET amplification, EML4-AL, KRAS G12C point mutations, RET rearrangements, HER2 amplification and mutations, and FGFR amplification and translocations. A re-biopsy at the time of tumor recurrence or progression after first-line treatment failure is important for further molecular assessment and personalized therapy. However, repeat tumor biopsies are fraught with challenges including access to the tumor, sample inadequacy, patient consent, patient performance status, safety, or physician's choice or assessment. Cytological specimens are gaining importance but are limited due to validation difficulties. Liquid biopsies, which are minimally invasive have shown promise to assess dynamic biomarkers using ctDNA analysis and are thus frequently considered in routine clinical practice in advanced NSCLC patients to guide further targeted treatment. Here we present a comprehensive review that emphasizes the significance of performing tumor re-biopsy in advanced stage NSCLC patients following resistance to first-line treatment and simultaneously highlights the current challenges in performing the same and the current status and future perspectives of liquid biopsy in NSCLC.

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Impact of Cytological Sampling on EGFR Mutation Testing in Stage III-IV Lung Adenocarcinoma

Cited by 6 publications

References 15 publications

Epidermal Growth Factor Receptor Mutation Frequency in Squamous Cell Carcinoma and Its Diagnostic Performance in Cytological Samples: A Molecular and Immunohistochemical Study

Epidermal Growth Factor Receptor Mutation Frequency in Squamous Cell Carcinoma and Its Diagnostic Performance in Cytological Samples: A Molecular and Immunohistochemical Study

Afatinib for the treatment of EGFR mutation-positive NSCLC: A review of clinical findings

Molecular Therapeutics of Non-Small Cell Lung Cancer (NSCLC) and Challenges in Repeat Tissue Biopsy

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