Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers
Abstract DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single as...
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Nature Portfolio
2016
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oai:doaj.org-article:0d55a397502a4dbe956a6fd30cff0c292021-12-02T16:08:01ZClinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers10.1038/s41598-016-0021-42045-2322https://doaj.org/article/0d55a397502a4dbe956a6fd30cff0c292016-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-016-0021-4https://doaj.org/toc/2045-2322Abstract DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1–3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.Mitesh J. BoradJan B. EganRachel M. CondjellaWinnie S. LiangRafael FonsecaNicole R. RitaccaAnn E. McCulloughMichael T. BarrettKatherine S. HuntMia D. ChampionMaitray D. PatelScott W. YoungAlvin C. SilvaThai H. HoThorvardur R. HalfdanarsonRobert R. McWilliamsKonstantinos N. LazaridisRamesh K. RamanathanAngela BakerJessica AldrichAhmet KurdogluTyler IzattAlexis ChristoforidesIrene CherniSara NasserRebecca ReimanLori CuyuganJacquelyn McDonaldJonathan AdkinsStephen D. MastrianRiccardo ValdezDawn E. JaroszewskiDaniel D. Von HoffDavid W. CraigA. Keith StewartJohn D. CarptenAlan H. BryceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 6, Iss 1, Pp 1-12 (2016) |
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Medicine R Science Q Mitesh J. Borad Jan B. Egan Rachel M. Condjella Winnie S. Liang Rafael Fonseca Nicole R. Ritacca Ann E. McCullough Michael T. Barrett Katherine S. Hunt Mia D. Champion Maitray D. Patel Scott W. Young Alvin C. Silva Thai H. Ho Thorvardur R. Halfdanarson Robert R. McWilliams Konstantinos N. Lazaridis Ramesh K. Ramanathan Angela Baker Jessica Aldrich Ahmet Kurdoglu Tyler Izatt Alexis Christoforides Irene Cherni Sara Nasser Rebecca Reiman Lori Cuyugan Jacquelyn McDonald Jonathan Adkins Stephen D. Mastrian Riccardo Valdez Dawn E. Jaroszewski Daniel D. Von Hoff David W. Craig A. Keith Stewart John D. Carpten Alan H. Bryce Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers |
| description |
Abstract DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1–3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets. |
| format |
article |
| author |
Mitesh J. Borad Jan B. Egan Rachel M. Condjella Winnie S. Liang Rafael Fonseca Nicole R. Ritacca Ann E. McCullough Michael T. Barrett Katherine S. Hunt Mia D. Champion Maitray D. Patel Scott W. Young Alvin C. Silva Thai H. Ho Thorvardur R. Halfdanarson Robert R. McWilliams Konstantinos N. Lazaridis Ramesh K. Ramanathan Angela Baker Jessica Aldrich Ahmet Kurdoglu Tyler Izatt Alexis Christoforides Irene Cherni Sara Nasser Rebecca Reiman Lori Cuyugan Jacquelyn McDonald Jonathan Adkins Stephen D. Mastrian Riccardo Valdez Dawn E. Jaroszewski Daniel D. Von Hoff David W. Craig A. Keith Stewart John D. Carpten Alan H. Bryce |
| author_facet |
Mitesh J. Borad Jan B. Egan Rachel M. Condjella Winnie S. Liang Rafael Fonseca Nicole R. Ritacca Ann E. McCullough Michael T. Barrett Katherine S. Hunt Mia D. Champion Maitray D. Patel Scott W. Young Alvin C. Silva Thai H. Ho Thorvardur R. Halfdanarson Robert R. McWilliams Konstantinos N. Lazaridis Ramesh K. Ramanathan Angela Baker Jessica Aldrich Ahmet Kurdoglu Tyler Izatt Alexis Christoforides Irene Cherni Sara Nasser Rebecca Reiman Lori Cuyugan Jacquelyn McDonald Jonathan Adkins Stephen D. Mastrian Riccardo Valdez Dawn E. Jaroszewski Daniel D. Von Hoff David W. Craig A. Keith Stewart John D. Carpten Alan H. Bryce |
| author_sort |
Mitesh J. Borad |
| title |
Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers |
| title_short |
Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers |
| title_full |
Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers |
| title_fullStr |
Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers |
| title_full_unstemmed |
Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers |
| title_sort |
clinical implementation of integrated genomic profiling in patients with advanced cancers |
| publisher |
Nature Portfolio |
| publishDate |
2016 |
| url |
https://doaj.org/article/0d55a397502a4dbe956a6fd30cff0c29 |
| work_keys_str_mv |
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