The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers

Background Mutations of the epidermal growth factor hormone receptor ( EGFR ) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identi...

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Veröffentlicht in:The Annals of thoracic surgery 2013-09, Vol.96 (3), p.962-968
Hauptverfasser: Izar, Benjamin, MD, PhD, Sequist, Lecia, MD, MPH, Lee, Mihan, BS, Muzikansky, Alona, PhD, Heist, Rebecca, MD, MPH, Iafrate, John, MD, PhD, Dias-Santagata, Dora, PhD, Mathisen, Douglas, MD, Lanuti, Michael, MD
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container_issue 3
container_start_page 962
container_title The Annals of thoracic surgery
container_volume 96
creator Izar, Benjamin, MD, PhD
Sequist, Lecia, MD, MPH
Lee, Mihan, BS
Muzikansky, Alona, PhD
Heist, Rebecca, MD, MPH
Iafrate, John, MD, PhD
Dias-Santagata, Dora, PhD
Mathisen, Douglas, MD
Lanuti, Michael, MD
description Background Mutations of the epidermal growth factor hormone receptor ( EGFR ) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy. Methods Mutation status was tested in treatment-naïve patients who had complete resection of stage I (T1–2a N0 ) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction–based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR -mutant and wild-type patients using Kaplan-Meier methods and Cox regression models. Results Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p  = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p  = 0.0085), and improved overall 5-year survival (98% versus 73%; p  = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p  = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation ( p  = 0.026) and tumor size less than 2 cm ( p  = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not. Conclusions Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC.
doi_str_mv 10.1016/j.athoracsur.2013.05.091
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However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy. Methods Mutation status was tested in treatment-naïve patients who had complete resection of stage I (T1–2a N0 ) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction–based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR -mutant and wild-type patients using Kaplan-Meier methods and Cox regression models. Results Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p  = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p  = 0.0085), and improved overall 5-year survival (98% versus 73%; p  = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p  = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation ( p  = 0.026) and tumor size less than 2 cm ( p  = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not. Conclusions Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC.</description><identifier>ISSN: 0003-4975</identifier><identifier>EISSN: 1552-6259</identifier><identifier>DOI: 10.1016/j.athoracsur.2013.05.091</identifier><identifier>PMID: 23932319</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Age Factors ; Aged ; Biomarkers, Tumor - genetics ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - surgery ; Cardiothoracic Surgery ; Cohort Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Lung Neoplasms - surgery ; Male ; Middle Aged ; Multivariate Analysis ; Mutation ; Neoplasm Invasiveness - pathology ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - mortality ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, Epidermal Growth Factor - genetics ; Retrospective Studies ; Risk Assessment ; Sex Factors ; Statistics, Nonparametric ; Surgery ; Survival Analysis</subject><ispartof>The Annals of thoracic surgery, 2013-09, Vol.96 (3), p.962-968</ispartof><rights>The Society of Thoracic Surgeons</rights><rights>2013 The Society of Thoracic Surgeons</rights><rights>Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-daf616e8227385f1f34b4cb37cdbc48e89b0655242d9ff2619af965b09b9fab43</citedby><cites>FETCH-LOGICAL-c429t-daf616e8227385f1f34b4cb37cdbc48e89b0655242d9ff2619af965b09b9fab43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23932319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Izar, Benjamin, MD, PhD</creatorcontrib><creatorcontrib>Sequist, Lecia, MD, MPH</creatorcontrib><creatorcontrib>Lee, Mihan, BS</creatorcontrib><creatorcontrib>Muzikansky, Alona, PhD</creatorcontrib><creatorcontrib>Heist, Rebecca, MD, MPH</creatorcontrib><creatorcontrib>Iafrate, John, MD, PhD</creatorcontrib><creatorcontrib>Dias-Santagata, Dora, PhD</creatorcontrib><creatorcontrib>Mathisen, Douglas, MD</creatorcontrib><creatorcontrib>Lanuti, Michael, MD</creatorcontrib><title>The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers</title><title>The Annals of thoracic surgery</title><addtitle>Ann Thorac Surg</addtitle><description>Background Mutations of the epidermal growth factor hormone receptor ( EGFR ) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy. Methods Mutation status was tested in treatment-naïve patients who had complete resection of stage I (T1–2a N0 ) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction–based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR -mutant and wild-type patients using Kaplan-Meier methods and Cox regression models. Results Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p  = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p  = 0.0085), and improved overall 5-year survival (98% versus 73%; p  = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p  = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation ( p  = 0.026) and tumor size less than 2 cm ( p  = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not. Conclusions Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. 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Sequist, Lecia, MD, MPH ; Lee, Mihan, BS ; Muzikansky, Alona, PhD ; Heist, Rebecca, MD, MPH ; Iafrate, John, MD, PhD ; Dias-Santagata, Dora, PhD ; Mathisen, Douglas, MD ; Lanuti, Michael, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-daf616e8227385f1f34b4cb37cdbc48e89b0655242d9ff2619af965b09b9fab43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Age Factors</topic><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - surgery</topic><topic>Cardiothoracic Surgery</topic><topic>Cohort Studies</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - surgery</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Mutation</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Neoplasm Staging</topic><topic>Proportional Hazards Models</topic><topic>Receptor, Epidermal Growth Factor - genetics</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Sex Factors</topic><topic>Statistics, Nonparametric</topic><topic>Surgery</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Izar, Benjamin, MD, PhD</creatorcontrib><creatorcontrib>Sequist, Lecia, MD, MPH</creatorcontrib><creatorcontrib>Lee, Mihan, BS</creatorcontrib><creatorcontrib>Muzikansky, Alona, PhD</creatorcontrib><creatorcontrib>Heist, Rebecca, MD, MPH</creatorcontrib><creatorcontrib>Iafrate, John, MD, PhD</creatorcontrib><creatorcontrib>Dias-Santagata, Dora, PhD</creatorcontrib><creatorcontrib>Mathisen, Douglas, MD</creatorcontrib><creatorcontrib>Lanuti, Michael, MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Annals of thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Izar, Benjamin, MD, PhD</au><au>Sequist, Lecia, MD, MPH</au><au>Lee, Mihan, BS</au><au>Muzikansky, Alona, PhD</au><au>Heist, Rebecca, MD, MPH</au><au>Iafrate, John, MD, PhD</au><au>Dias-Santagata, Dora, PhD</au><au>Mathisen, Douglas, MD</au><au>Lanuti, Michael, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers</atitle><jtitle>The Annals of thoracic surgery</jtitle><addtitle>Ann Thorac Surg</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>96</volume><issue>3</issue><spage>962</spage><epage>968</epage><pages>962-968</pages><issn>0003-4975</issn><eissn>1552-6259</eissn><abstract>Background Mutations of the epidermal growth factor hormone receptor ( EGFR ) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy. Methods Mutation status was tested in treatment-naïve patients who had complete resection of stage I (T1–2a N0 ) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction–based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR -mutant and wild-type patients using Kaplan-Meier methods and Cox regression models. Results Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p  = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p  = 0.0085), and improved overall 5-year survival (98% versus 73%; p  = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p  = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation ( p  = 0.026) and tumor size less than 2 cm ( p  = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not. Conclusions Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>23932319</pmid><doi>10.1016/j.athoracsur.2013.05.091</doi><tpages>7</tpages></addata></record>
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subjects Age Factors
Aged
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - surgery
Cardiothoracic Surgery
Cohort Studies
Disease-Free Survival
Female
Humans
Kaplan-Meier Estimate
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Lung Neoplasms - surgery
Male
Middle Aged
Multivariate Analysis
Mutation
Neoplasm Invasiveness - pathology
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - mortality
Neoplasm Staging
Proportional Hazards Models
Receptor, Epidermal Growth Factor - genetics
Retrospective Studies
Risk Assessment
Sex Factors
Statistics, Nonparametric
Surgery
Survival Analysis
title The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers
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