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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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. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC.</description><subject>Age Factors</subject><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - surgery</subject><subject>Cardiothoracic Surgery</subject><subject>Cohort Studies</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - surgery</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Staging</subject><subject>Proportional Hazards Models</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Sex Factors</subject><subject>Statistics, Nonparametric</subject><subject>Surgery</subject><subject>Survival Analysis</subject><issn>0003-4975</issn><issn>1552-6259</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvhLyAfuST4I8nGFyRYtaXSQlG3iKPlOOOulyRebAep_56JtoDEiYvH1rzzjucZQihnJWe8eXsoTd6HaGyaYykYlyWrS6b4E7LidS2KRtTqKVkxxmRRqXV9Rl6kdMCnwPRzciakkkJytSLD3R7o9Xg0NtPg6MXV5S39NGeTfZjoDuOcKN5u5mzDCIn6iX7BJEw50W8-7-ktJLAZ-kV8j1b0c5iK3WiGgW4Aj-083dONmSzE9JI8c2ZI8OoxnpOvlxd3m4_F9ubqevN-W9hKqFz0xjW8gVaItWxrx52susp2cm37zlYttKpjDY5ZiV45JxqujFNN3THVKWe6Sp6TNyffYww_ZkhZjz5Z_I2ZIMxJc2zTSI5kUNqepDaGlCI4fYx-NPFBc6YX1vqg_7LWC2vNao2ssfT1Y5e5G6H_U_gbLgo-nASAs_70EHWySM5C7yMy033w_9Pl3T8mdvCTt2b4Dg-QDmGOE7LUXCehmd4tO19WziXjohaN_AW12qlo</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Izar, Benjamin, MD, PhD</creator><creator>Sequist, Lecia, MD, MPH</creator><creator>Lee, Mihan, BS</creator><creator>Muzikansky, Alona, PhD</creator><creator>Heist, Rebecca, MD, MPH</creator><creator>Iafrate, John, MD, PhD</creator><creator>Dias-Santagata, Dora, PhD</creator><creator>Mathisen, Douglas, MD</creator><creator>Lanuti, Michael, MD</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130901</creationdate><title>The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers</title><author>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</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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