An Alternative Approach to Determining Therapeutic Choices in Advanced Non-small Cell Lung Carcinoma (NSCLC): Maximizing the Diagnostic Procedure and the Use of Low-Volume Lung Biopsies

Lim, Elaine; Zhang, Shen Li; Yu, Kun; Nga, Min En; Ahmed, Dokeu A.; Agasthian, Thirugnanam; Wong, Poo Sing; Chua, Gim Chuah; Wong, Daniel; Tan, Lenny; Seto, Kar Yin; Yap, Wee See; Low, Seow Ping; Khoo, Kong Soo; Chang, Alex; Ng, Alan

doi:10.1097/01.jto.0000268671.49378.c2

Cited by 16 publications

(19 citation statements)

References 22 publications

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“…Several recent studies have demonstrated that expression of certain genes is associated with response to cisplatin-based therapy and survival [14][15][16]. Moreover, by utilising transbronchial needle lymph node aspiration samples, several groups have shown that evaluation of the epidermal growth factor receptor status can be performed [17][18][19][20]. Therefore, with adjustable-depth endobronchial ultrasound needle transbronchial needle lymph node aspiration, the potential may exist for greater tissue acquisition to be used for molecular and genetic analysis to guide therapy in unresectable patients, but at the potential cost of increased infection risk.…”

Section: Infectious Complications From Ebus-tbna Ar Haasmentioning

confidence: 99%

Infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration

2009

Eur Respir J

109

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The development of a convex probe endobronchial ultrasound (CP-EBUS) videobronchoscope to allow real-time transbronchial needle aspiration (TBNA) has been a significant advance in minimally invasive lung cancer staging and diagnosis. Several recent studies have demonstrated CP-EBUS-TBNA to have recovery rivalling that of the current gold standard, cervical mediastinoscopy. These same studies have indicated that the safety of this procedure has no reported complications.The present case study presents two infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration and discusses possible aetiologies of these infections, as well as implications for future application of this technology.

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Section: Infectious Complications From Ebus-tbna Ar Haasmentioning

confidence: 99%

Infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration

2009

Eur Respir J

109

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“…A variety of PCR methods, increasingly real time PCR (Q-PCR) targeted mutation detection assays, are currently applied for diagnostic KRAS mutation assessments [20], [21], some of which have already acquired the license for in vitro diagnostic (IVD) use in Europe [22]. These methods are developed to overcome the shortcomings of conventional dideoxy-sequencing, the as yet golden standard for mutation assessment, namely labor, time and expertise requirements, low sensitivity at 30% detection of mutant cells in tissues and variously low efficiency on FFPE-DNA [23], [24]. Indeed, Q-PCR methods are easy, fast and surpass the requirement of “1% sensitivity” set for diagnostic mutation assessments [21], while the infrastructure necessary to perform these tests is increasingly acquired in diagnostic laboratories.…”

Section: Introductionmentioning

confidence: 99%

Targeted KRAS Mutation Assessment on Patient Tumor Histologic Material in Real Time Diagnostics

et al. 2009

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BackgroundTesting for tumor specific mutations on routine formalin-fixed paraffin-embedded (FFPE) tissues may predict response to treatment in Medical Oncology and has already entered diagnostics, with KRAS mutation assessment as a paradigm. The highly sensitive real time PCR (Q-PCR) methods developed for this purpose are usually standardized under optimal template conditions. In routine diagnostics, however, suboptimal templates pose the challenge. Herein, we addressed the applicability of sequencing and two Q-PCR methods on prospectively assessed diagnostic cases for KRAS mutations.Methodology/Principal FindingsTumor FFPE-DNA from 135 diagnostic and 75 low-quality control samples was obtained upon macrodissection, tested for fragmentation and assessed for KRAS mutations with dideoxy-sequencing and with two Q-PCR methods (Taqman-minor-groove-binder [TMGB] probes and DxS-KRAS-IVD). Samples with relatively well preserved DNA could be accurately analyzed with sequencing, while Q-PCR methods yielded informative results even in cases with very fragmented DNA (p<0.0001) with 100% sensitivity and specificity vs each other. However, Q-PCR efficiency (Ct values) also depended on DNA-fragmentation (p<0.0001). Q-PCR methods were sensitive to detect ≤1% mutant cells, provided that samples yielded cycle thresholds (Ct) <29, but this condition was met in only 38.5% of diagnostic samples. In comparison, FFPE samples (>99%) could accurately be analyzed at a sensitivity level of 10% (external validation of TMGB results). DNA quality and tumor cell content were the main reasons for discrepant sequencing/Q-PCR results (1.5%).Conclusions/SignificanceDiagnostic targeted mutation assessment on FFPE-DNA is very efficient with Q-PCR methods in comparison to dideoxy-sequencing. However, DNA fragmentation/amplification capacity and tumor DNA content must be considered for the interpretation of Q-PCR results in order to provide accurate information for clinical decision making.

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“…These tumour specimens were stored as either paraffin-embedded tissues10 15 40 42 43 61–63 65–67 70–77 81–83 or snap-frozen samples,15 35 64 68 69 78 84 85 or analysed as fresh tissue 79. Fine-needle aspirates (FNAs),86–88 bronchial brushings, serum and plasma, circulating tumour cells (CTCs) and pleural effusion samples have also been used to assess EGFR mutation status in patients receiving EGFR TKI therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Lim and colleagues were able to obtain sufficient genomic DNA for genotypic assessment from more than 80% of their 24 low-volume samples (needle or forceps biopsy or fine-needle aspiration) 79. Of the 139 patients studied by Shih and colleagues,72 only two had insufficient DNA for analysis, whereas Savic and colleagues80 successfully sequenced the DNA from 93% of their 84 cytological NSCLC specimens.…”

Section: Introductionmentioning

confidence: 99%

“…A recent comparative study by Querings et al demonstrated that dideoxy ‘Sanger’ sequencing is less sensitive than pyrosequencing 100. Mutations have been identified in DNA provided by both PCR amplification and real-time quantitative PCR (qPCR) and also in genomic DNA 79 81. Both PCR amplification10 15 35 40 42 43 61–68 71–73 76 78–80 82–84 89 101–103 and qPCR40 69 83 89 104 limit the detection of mutations to those within the amplified region.…”

Section: Introductionmentioning

confidence: 99%

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The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC: Figure 1

et al. 2011

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The majority of patients with non-small-cell lung cancer (NSCLC) present with advanced disease, with targeted therapies providing some improvement in clinical outcomes. The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. Tyrosine kinase inhibitors (TKIs), which target the EGFR TK domain, have proven to be an effective treatment strategy; however, patient responses to treatment vary considerably. Therefore, the identification of patients most likely to respond to treatment is essential to optimise the benefit of TKIs. Tumour-associated activating mutations inEGFRcan identify patients with NSCLC who are likely to have a good response to TKIs. Nonetheless, the majority of patients relapse within a year of starting treatment. Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of theEGFRTK domain in approximately 50% of cases. Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/pan-erb inhibitors. A number of techniques have been employed for genotypic assessment of tumour-associated DNA to identifyEGFRmutations, each of which has advantages and disadvantages. This review presents an overview of the current methodologies used to identify such molecular markers. Recent developments in technology may make the monitoring of changes in patients' tumour genotypes easier in clinical practice, which may enable patients' treatment regimens to be tailored during the course of their disease, potentially leading to improved patient outcomes.

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An Alternative Approach to Determining Therapeutic Choices in Advanced Non-small Cell Lung Carcinoma (NSCLC): Maximizing the Diagnostic Procedure and the Use of Low-Volume Lung Biopsies

Abstract: Acquiring a separate low-volume lung biopsy sample for mutational analysis in lung cancer patients during the diagnostic procedure is feasible and may be a valuable complement to the usual diagnostic workflow in future.

Cited by 16 publications

References 22 publications

Infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration

Infectious complications from full extension endobronchial ultrasound transbronchial needle aspiration

Targeted KRAS Mutation Assessment on Patient Tumor Histologic Material in Real Time Diagnostics

The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC: Figure 1

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