The Introduction of Systematic Genomic Testing for Patients with Non–Small-Cell Lung Cancer

Cardarella, Stephanie; Ortiz, Taylor M.; Joshi, Victoria A.; Butaney, Mohit; Jackman, David M.; Kwiatkowski, David J.; Yeap, Beow Y.; Jänne, Pasi A.; Lindeman, Neal I.; Johnson, Bruce E.

doi:10.1097/jto.0b013e3182745bcb

Cited by 95 publications

(87 citation statements)

References 28 publications

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“…Testing for ALK gene rearrangements can be performed with FISH or with NGS if the platform is validated and can identify gene fusions. 51,126,207 For the 2017 update (Version 1), the NCCN panel also added a recommendation for upfront PD-L1 expression testing before first-line therapy in patients with metastatic NSCLC to assess whether patients are candidates for immune checkpoint inhibitors (see "Pembrolizumab," page 523).…”

Section: Treatment Of Recurrences and Distant Metastasesmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,114

1,005

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Section: Treatment Of Recurrences and Distant Metastasesmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,114

1,005

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show abstract

“…Systematic genotyping for KRAS mutations for all advanced nonsquamous NSCLC was initiated at DFCI in 2008 and is performed in a CLIA-certified laboratory (32). We manually reviewed the list of the selected cases and the staging workup at the time the patient was identified to have systemic disease.…”

Section: Study Populationmentioning

confidence: 99%

“…We identified patients with KRAS-mutant NSCLC through an institutional database of patients that had undergone genotyping as previously described (31,32). Systematic genotyping for KRAS mutations for all advanced nonsquamous NSCLC was initiated at DFCI in 2008 and is performed in a CLIA-certified laboratory (32).…”

Section: Study Populationmentioning

confidence: 99%

Immunohistochemical Loss of LKB1 Is a Biomarker for More Aggressive Biology in KRAS-Mutant Lung Adenocarcinoma

Calles

Sholl

Rodig

et al. 2015

Clinical Cancer Research

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Purpose: LKB1 loss is common in lung cancer, but no assay exists to efficiently evaluate the presence or absence of LKB1. We validated an IHC assay for LKB1 loss and determined the impact of LKB1 loss in KRAS-mutant non-small cell lung cancer (NSCLC).Experimental Design: We optimized and validated an IHC assay for LKB1 (clone Ley37D/G6) using a panel of lung cancer cell lines and tumors with known LKB1 mutations, including 2 patients with Peutz-Jeghers syndrome (PJS) who developed lung adenocarcinoma. We retrospectively analyzed tumors for LKB1 using IHC from 154 KRAS-mutant NSCLC patients, including 123 smokers and 31 never-smokers, and correlated the findings with patient and tumor characteristics and clinical outcome.Results: LKB1 expression was lost by IHC in 30% of KRASmutant NSCLC (smokers 35% vs. never-smokers 13%, P ¼ 0.017). LKB1 loss did not correlate with a specific KRAS mutation but was more frequent in tumors with KRAS transversion mutations (P ¼ 0.029). KRAS-mutant NSCLC patients with concurrent LKB1 loss had a higher number of metastatic sites at the time of diagnosis (median 2.5 vs. 2, P ¼ 0.01), higher incidence of extrathoracic metastases (P ¼ 0.01), and developed brain metastasis more frequently (48% vs. 25%, P ¼ 0.02). There was a nonsignificant trend to worse survival in stage IV KRAS-mutant NSCLC patients with LKB1 loss.Conclusions: LKB1 IHC is a reliable and efficient assay to evaluate for loss of LKB1 in clinical samples of NSCLC. LKB1 loss is more common in smokers, and is associated with a more aggressive clinical phenotype in KRAS-mutant NSCLC patients, accordingly to preclinical models.

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“…Somatic mutation analysis of known or potential druggable oncogenes has gradually become part of the routine practice in thoracic oncology (1,2). In non-small cell lung cancer (NSCLC), the type of somatic mutations and the genes affected are related to smoking status.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers: A Proof-of-Concept Study from BioCAST/IFCT-1002

Couraud

Vaca-Paniagua

Villar

et al. 2014

Clinical Cancer Research

197

155

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Purpose: Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations.Experimental Design: A total of 107 plasma samples were collected from the BioCAST/IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2, and PI3KCA genes, and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent Personal Genome Machine Platform.Results: CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% (95% confidence interval, 43%-71%) and the estimated specificity was 87% (62%-96%).Conclusion: These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer. Clin Cancer Res; 20(17); 4613-24. Ó2014 AACR.

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The Introduction of Systematic Genomic Testing for Patients with Non–Small-Cell Lung Cancer

Cited by 95 publications

References 28 publications

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Immunohistochemical Loss of LKB1 Is a Biomarker for More Aggressive Biology in KRAS-Mutant Lung Adenocarcinoma

Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers: A Proof-of-Concept Study from BioCAST/IFCT-1002

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