<i>EGFR</i> Mutations Predict Survival Benefit From Gefitinib in Patients With Advanced Lung Adenocarcinoma: A Historical Comparison of Patients Treated Before and After Gefitinib Approval in Japan

Takano, Toshimi; Fukui, Tomoya; Ohe, Yuichiro; Tsuta, Koji; Yamamoto, Seiichiro; Nokihara, Hiroshi; Yamamoto, Noboru; Sekine, Ikuo; Kunitoh, Hideo; Furuta, Koh; Tamura, Tomohide

doi:10.1200/jco.2008.16.7254

Cited by 202 publications

(128 citation statements)

References 32 publications

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“…TAKANO et al [30] showed that patients with lung cancer treated after the approval of gefitinib had longer overall survival than those treated before gefitinib We previously showed that patients with MPEs associated with lung adenocarcinoma had a higher EGFR mutation rate than that observed in surgically resected specimens [3]. With more patients enrolled in the present study, we found that the overall EGFR mutation rate was similar to that in our previous report [3].…”

Section: Discussionsupporting

confidence: 87%

Survival of lung adenocarcinoma patients with malignant pleural effusion

Tsai

et al. 2012

Eur Respir J

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In the era of targeted therapy, the association between lung adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene (EGFR) mutation status of lung adenocarcinoma patients with MPE.From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics, EGFR mutation status, and overall survival were analysed.We collected MPEs from 448 patients in stage IV lung adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p50.001). There were 296 (66.1%) patients harbouring EGFR mutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p50.044); the L858R mutation rate was also higher among the former (32.6% versus 18.1%; p50.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harboured EGFR mutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV lung adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higher EGFR mutation rate, especially for L858R, than patients who develop MPEs following disease progression.

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Section: Discussionsupporting

confidence: 87%

Survival of lung adenocarcinoma patients with malignant pleural effusion

Tsai

et al. 2012

Eur Respir J

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“…Additionally, melt profiles triage regions where sequence variation is not present, thus reducing the cost of sequencing and the time required for its interpretation. HRM has identified somatic mutation in primary tumor tissue and formalinfixed paraffin-embedded histological specimens [Do et al, 2008;Fukui et al, 2008;Simi et al, 2008;Takano et al, 2008]. Identifying somatic mutations in tumor tissue is similar to identifying heteroplasmic variants in mtDNA.…”

Section: Discussionmentioning

confidence: 99%

Identifying sequence variants in the human mitochondrial genome using high-resolution melt (HRM) profiling

Dobrowolski¹,

Hendrickx

Bosch

et al. 2009

Hum. Mutat.

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Identifying mitochondrial DNA (mtDNA) sequence variants in human diseases is complicated. Many pathological mutations are heteroplasmic, with the mutant allele represented at highly variable percentages. Highresolution melt (HRM or HRMA) profiling was applied to comprehensive assessment of the mitochondrial genome and targeted assessment of recognized pathological mutations. The assay panel providing comprehensive coverage of the mitochondrial genome utilizes 36 overlapping fragments (301-658 bp) that employ a common PCR protocol. The comprehensive assay identified heteroplasmic mutation in 33 out of 33 patient specimens tested. Allele fraction among the specimens ranged from 1 to 100%. The comprehensive assay panel was also used to assess 125 mtDNA specimens from healthy donors, which identified 431 unique sequence variants. Utilizing the comprehensive mtDNA panel, the mitochondrial genome of a patient specimen may be assessed in less than 1 day using a single 384-well plate or two 96-well plates. Specific assays were used to identify the myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) mutation m.3243A4G, myoclonus epilepsy, ragged red fibers (MERRF) mutation m.8344A4G, and m.1555A4G associated with aminoglycoside hearing loss. These assays employ a calibrated, amplicon-based strategy that is exceedingly simple in design, utilization, and interpretation, yet provides sensitivity to detect variants at and below 10% heteroplasmy. Turnaround time for the genotyping tests is about 1 hr.

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“…To improve the prognosis of patients with LCNEC, understanding the clinicopathological features and the effectiveness of treatment in patients with LCNEC is imperative. Recent reports have revealed the effectiveness of molecular-targeted therapy in patients with lung adenocarcinoma (AC) (4,5). Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) has been effective for NSCLC, particularly in patients with lung AC and specific EGFR mutations in exon 19 or exon 21, or Asian patients (4).…”

Section: Introductionmentioning

confidence: 99%

Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma

Iyoda

Travis

Sarkaria

et al. 2011

Experimental and Therapeutic Medicine

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EGFR Mutations Predict Survival Benefit From Gefitinib in Patients With Advanced Lung Adenocarcinoma: A Historical Comparison of Patients Treated Before and After Gefitinib Approval in Japan

Abstract: EGFR mutations significantly predict both a survival benefit from gefitinib and a favorable prognosis in patients with advanced lung adenocarcinoma.

Cited by 202 publications

References 32 publications

Survival of lung adenocarcinoma patients with malignant pleural effusion

Survival of lung adenocarcinoma patients with malignant pleural effusion

Identifying sequence variants in the human mitochondrial genome using high-resolution melt (HRM) profiling

Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma

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