Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism‐Driven Clinical Trials
Background. The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of...
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| Veröffentlicht in: | The oncologist (Dayton, Ohio) Ohio), 2016-06, Vol.21 (6), p.684-691 |
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| creator | Suh, James H. Johnson, Adrienne Albacker, Lee Wang, Kai Chmielecki, Juliann Frampton, Garrett Gay, Laurie Elvin, Julia A. Vergilio, Jo‐Anne Ali, Siraj Miller, Vincent A. Stephens, Philip J. Ross, Jeffrey S. |
| description | Background.
The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture‐based next‐generation sequencing (NGS) test, in clinical practice.
Methods.
CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012–2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes.
Results.
The median age of the patients was 64 years (range: 13–88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer‐related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%).
Conclusion.
CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with “pan‐negative” lung AD who may benefit from enrollment in mechanism‐driven clinical trials.
Implications for Practice:
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases. Although logistical and administrative hurdles limit the widespread use of next‐generation sequencing, the data confirm the feasibility and potential utility of comprehensive genomic profiling in clinical practice.
National Comprehensive Cancer N |
| doi_str_mv | 10.1634/theoncologist.2016-0030 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4912374</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1797869230</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4674-fc6e814b295ae202c5f17a84f5c1dc209dd559d86b75d198f3185a52f783c9e83</originalsourceid><addsrcrecordid>eNqNUstuEzEUHSEQLYVfAC_ZTLFn7HksQKJDGyKlSRdBsLMcz3ViOmMHe9IqOz6Bb-QT-AJuSKjIjtW91z73nGPrJMkrRs9ZkfM3wwq8077zSxuH84yyIqU0p4-SUyZ4nfKafnmMPa3ytGSiPkmexfiVUmzz7GlykuEhKwQ_TX41vl8HWIGL9g7ICJzvrSY3wRvbWbckV0pjM6gBIhn36w56cDhZ74g3BH2Q6Z9JdeSYqlFOQyBTGO59uCWjjW0BGZHG-EAmG-Q-QC6s71W4xW4OcdiJKteScYtC1lhcuEEFHCL5vPLkWm3JBTgwdiBXwffk0gXfdTtbxDpyDXqlnI39z-8_PgQ04kiDslajwXmwqovPkycGC7w41LPk09XlvPmYTmajcfN-kmpelDw1uoCK8UVWCwUZzbQwrFQVN0KzVme0blsh6rYqFqVoWV2ZnFVCicyUVa5rqPKz5N2ed71Z9NBqNBhUJ9fB4mu30isrj2-cXcmlv5O8ZlleciR4fSAI_tsGv0b2NmroOuXAb6JkZV1WRZ3lFKHlHqqDjzGAeZBhVO4SI48SI3eJkbvE4ObLf10-7P2NCALe7gH3toPt__LK2bSZ0aLi-W8j2N4_</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1797869230</pqid></control><display><type>article</type><title>Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism‐Driven Clinical Trials</title><source>MEDLINE</source><source>Wiley Online Library</source><source>Open Access: Oxford University Press Open Journals</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Suh, James H. ; Johnson, Adrienne ; Albacker, Lee ; Wang, Kai ; Chmielecki, Juliann ; Frampton, Garrett ; Gay, Laurie ; Elvin, Julia A. ; Vergilio, Jo‐Anne ; Ali, Siraj ; Miller, Vincent A. ; Stephens, Philip J. ; Ross, Jeffrey S.</creator><creatorcontrib>Suh, James H. ; Johnson, Adrienne ; Albacker, Lee ; Wang, Kai ; Chmielecki, Juliann ; Frampton, Garrett ; Gay, Laurie ; Elvin, Julia A. ; Vergilio, Jo‐Anne ; Ali, Siraj ; Miller, Vincent A. ; Stephens, Philip J. ; Ross, Jeffrey S.</creatorcontrib><description>Background.
The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture‐based next‐generation sequencing (NGS) test, in clinical practice.
Methods.
CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012–2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes.
Results.
The median age of the patients was 64 years (range: 13–88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer‐related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%).
Conclusion.
CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with “pan‐negative” lung AD who may benefit from enrollment in mechanism‐driven clinical trials.
Implications for Practice:
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases. Although logistical and administrative hurdles limit the widespread use of next‐generation sequencing, the data confirm the feasibility and potential utility of comprehensive genomic profiling in clinical practice.
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases.</description><identifier>ISSN: 1083-7159</identifier><identifier>EISSN: 1549-490X</identifier><identifier>DOI: 10.1634/theoncologist.2016-0030</identifier><identifier>PMID: 27151654</identifier><language>eng</language><publisher>Durham, NC, USA: AlphaMed Press</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma of Lung ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung - genetics ; Clinical trials ; Clinical Trials as Topic ; Comprehensive genomic profiling ; ErbB Receptors - genetics ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Cancer ; Lung Neoplasms - genetics ; Middle Aged ; Mutation ; National Comprehensive Cancer Network guidelines ; Non‐small cell lung cancer ; Patient Participation ; Young Adult</subject><ispartof>The oncologist (Dayton, Ohio), 2016-06, Vol.21 (6), p.684-691</ispartof><rights>2016 AlphaMed Press</rights><rights>AlphaMed Press.</rights><rights>AlphaMed Press 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4674-fc6e814b295ae202c5f17a84f5c1dc209dd559d86b75d198f3185a52f783c9e83</citedby><cites>FETCH-LOGICAL-c4674-fc6e814b295ae202c5f17a84f5c1dc209dd559d86b75d198f3185a52f783c9e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912374/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912374/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,27901,27902,45550,45551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27151654$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suh, James H.</creatorcontrib><creatorcontrib>Johnson, Adrienne</creatorcontrib><creatorcontrib>Albacker, Lee</creatorcontrib><creatorcontrib>Wang, Kai</creatorcontrib><creatorcontrib>Chmielecki, Juliann</creatorcontrib><creatorcontrib>Frampton, Garrett</creatorcontrib><creatorcontrib>Gay, Laurie</creatorcontrib><creatorcontrib>Elvin, Julia A.</creatorcontrib><creatorcontrib>Vergilio, Jo‐Anne</creatorcontrib><creatorcontrib>Ali, Siraj</creatorcontrib><creatorcontrib>Miller, Vincent A.</creatorcontrib><creatorcontrib>Stephens, Philip J.</creatorcontrib><creatorcontrib>Ross, Jeffrey S.</creatorcontrib><title>Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism‐Driven Clinical Trials</title><title>The oncologist (Dayton, Ohio)</title><addtitle>Oncologist</addtitle><description>Background.
The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture‐based next‐generation sequencing (NGS) test, in clinical practice.
Methods.
CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012–2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes.
Results.
The median age of the patients was 64 years (range: 13–88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer‐related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%).
Conclusion.
CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with “pan‐negative” lung AD who may benefit from enrollment in mechanism‐driven clinical trials.
Implications for Practice:
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases. Although logistical and administrative hurdles limit the widespread use of next‐generation sequencing, the data confirm the feasibility and potential utility of comprehensive genomic profiling in clinical practice.
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma of Lung</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Clinical trials</subject><subject>Clinical Trials as Topic</subject><subject>Comprehensive genomic profiling</subject><subject>ErbB Receptors - genetics</subject><subject>Gene Expression Profiling</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Lung Cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>National Comprehensive Cancer Network guidelines</subject><subject>Non‐small cell lung cancer</subject><subject>Patient Participation</subject><subject>Young Adult</subject><issn>1083-7159</issn><issn>1549-490X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUstuEzEUHSEQLYVfAC_ZTLFn7HksQKJDGyKlSRdBsLMcz3ViOmMHe9IqOz6Bb-QT-AJuSKjIjtW91z73nGPrJMkrRs9ZkfM3wwq8077zSxuH84yyIqU0p4-SUyZ4nfKafnmMPa3ytGSiPkmexfiVUmzz7GlykuEhKwQ_TX41vl8HWIGL9g7ICJzvrSY3wRvbWbckV0pjM6gBIhn36w56cDhZ74g3BH2Q6Z9JdeSYqlFOQyBTGO59uCWjjW0BGZHG-EAmG-Q-QC6s71W4xW4OcdiJKteScYtC1lhcuEEFHCL5vPLkWm3JBTgwdiBXwffk0gXfdTtbxDpyDXqlnI39z-8_PgQ04kiDslajwXmwqovPkycGC7w41LPk09XlvPmYTmajcfN-kmpelDw1uoCK8UVWCwUZzbQwrFQVN0KzVme0blsh6rYqFqVoWV2ZnFVCicyUVa5rqPKz5N2ed71Z9NBqNBhUJ9fB4mu30isrj2-cXcmlv5O8ZlleciR4fSAI_tsGv0b2NmroOuXAb6JkZV1WRZ3lFKHlHqqDjzGAeZBhVO4SI48SI3eJkbvE4ObLf10-7P2NCALe7gH3toPt__LK2bSZ0aLi-W8j2N4_</recordid><startdate>201606</startdate><enddate>201606</enddate><creator>Suh, James H.</creator><creator>Johnson, Adrienne</creator><creator>Albacker, Lee</creator><creator>Wang, Kai</creator><creator>Chmielecki, Juliann</creator><creator>Frampton, Garrett</creator><creator>Gay, Laurie</creator><creator>Elvin, Julia A.</creator><creator>Vergilio, Jo‐Anne</creator><creator>Ali, Siraj</creator><creator>Miller, Vincent A.</creator><creator>Stephens, Philip J.</creator><creator>Ross, Jeffrey S.</creator><general>AlphaMed Press</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><scope>5PM</scope></search><sort><creationdate>201606</creationdate><title>Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism‐Driven Clinical Trials</title><author>Suh, James H. ; Johnson, Adrienne ; Albacker, Lee ; Wang, Kai ; Chmielecki, Juliann ; Frampton, Garrett ; Gay, Laurie ; Elvin, Julia A. ; Vergilio, Jo‐Anne ; Ali, Siraj ; Miller, Vincent A. ; Stephens, Philip J. ; Ross, Jeffrey S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4674-fc6e814b295ae202c5f17a84f5c1dc209dd559d86b75d198f3185a52f783c9e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma of Lung</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Clinical trials</topic><topic>Clinical Trials as Topic</topic><topic>Comprehensive genomic profiling</topic><topic>ErbB Receptors - genetics</topic><topic>Gene Expression Profiling</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Lung Cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>National Comprehensive Cancer Network guidelines</topic><topic>Non‐small cell lung cancer</topic><topic>Patient Participation</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suh, James H.</creatorcontrib><creatorcontrib>Johnson, Adrienne</creatorcontrib><creatorcontrib>Albacker, Lee</creatorcontrib><creatorcontrib>Wang, Kai</creatorcontrib><creatorcontrib>Chmielecki, Juliann</creatorcontrib><creatorcontrib>Frampton, Garrett</creatorcontrib><creatorcontrib>Gay, Laurie</creatorcontrib><creatorcontrib>Elvin, Julia A.</creatorcontrib><creatorcontrib>Vergilio, Jo‐Anne</creatorcontrib><creatorcontrib>Ali, Siraj</creatorcontrib><creatorcontrib>Miller, Vincent A.</creatorcontrib><creatorcontrib>Stephens, Philip J.</creatorcontrib><creatorcontrib>Ross, Jeffrey S.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The oncologist (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suh, James H.</au><au>Johnson, Adrienne</au><au>Albacker, Lee</au><au>Wang, Kai</au><au>Chmielecki, Juliann</au><au>Frampton, Garrett</au><au>Gay, Laurie</au><au>Elvin, Julia A.</au><au>Vergilio, Jo‐Anne</au><au>Ali, Siraj</au><au>Miller, Vincent A.</au><au>Stephens, Philip J.</au><au>Ross, Jeffrey S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism‐Driven Clinical Trials</atitle><jtitle>The oncologist (Dayton, Ohio)</jtitle><addtitle>Oncologist</addtitle><date>2016-06</date><risdate>2016</risdate><volume>21</volume><issue>6</issue><spage>684</spage><epage>691</epage><pages>684-691</pages><issn>1083-7159</issn><eissn>1549-490X</eissn><abstract>Background.
The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture‐based next‐generation sequencing (NGS) test, in clinical practice.
Methods.
CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012–2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes.
Results.
The median age of the patients was 64 years (range: 13–88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer‐related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%).
Conclusion.
CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with “pan‐negative” lung AD who may benefit from enrollment in mechanism‐driven clinical trials.
Implications for Practice:
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases. Although logistical and administrative hurdles limit the widespread use of next‐generation sequencing, the data confirm the feasibility and potential utility of comprehensive genomic profiling in clinical practice.
National Comprehensive Cancer Network guidelines for patients with metastatic non‐small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer‐related genes were altered in at least 0.1% of the AD cases.</abstract><cop>Durham, NC, USA</cop><pub>AlphaMed Press</pub><pmid>27151654</pmid><doi>10.1634/theoncologist.2016-0030</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - genetics Adenocarcinoma of Lung Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor Carcinoma, Non-Small-Cell Lung - genetics Clinical trials Clinical Trials as Topic Comprehensive genomic profiling ErbB Receptors - genetics Gene Expression Profiling High-Throughput Nucleotide Sequencing Humans Lung Cancer Lung Neoplasms - genetics Middle Aged Mutation National Comprehensive Cancer Network guidelines Non‐small cell lung cancer Patient Participation Young Adult |
| title | Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism‐Driven Clinical Trials |
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