Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers

Mitesh J Borad, Jan B. Egan, Rachel M. Condjella, Winnie S. Liang, Rafael Fonseca, Nicole R. Ritacca, Ann E. McCullough, Michael Barrett, Katherine S. Hunt, Mia D. Champion, Maitray D. Patel, Scott W. Young, Alvin C Silva, Thai H Ho, Thorvardur R. Halfdanarson, Robert R Mc Williams, Konstantinos N Lazaridis, Ramesk K Ramanathan, Angela Baker, Jessica AldrichAhmet 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, Alexander Keith Stewart, John D. Carpten, Alan H Bryce

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article number25
JournalScientific Reports
Volume6
Issue number1
DOIs
StatePublished - 2016

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Neoplasms
Therapeutics
DNA Fingerprinting
Patient Preference
Pharmaceutical Preparations
Research Design
Clinical Trials
Prospective Studies
RNA
Mutation
DNA

ASJC Scopus subject areas

  • General

Cite this

Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers. / Borad, Mitesh J; Egan, Jan B.; Condjella, Rachel M.; Liang, Winnie S.; Fonseca, Rafael; Ritacca, Nicole R.; McCullough, Ann E.; Barrett, Michael; Hunt, Katherine S.; Champion, Mia D.; Patel, Maitray D.; Young, Scott W.; Silva, Alvin C; Ho, Thai H; Halfdanarson, Thorvardur R.; Mc Williams, Robert R; Lazaridis, Konstantinos N; Ramanathan, Ramesk K; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Cuyugan, Lori; McDonald, Jacquelyn; Adkins, Jonathan; Mastrian, Stephen D.; Valdez, Riccardo; Jaroszewski, Dawn E.; Von Hoff, Daniel D.; Craig, David W.; Stewart, Alexander Keith; Carpten, John D.; Bryce, Alan H.

In: Scientific Reports, Vol. 6, No. 1, 25, 2016.

Research output: Contribution to journalArticle

Borad, MJ, Egan, JB, Condjella, RM, Liang, WS, Fonseca, R, Ritacca, NR, McCullough, AE, Barrett, M, Hunt, KS, Champion, MD, Patel, MD, Young, SW, Silva, AC, Ho, TH, Halfdanarson, TR, Mc Williams, RR, Lazaridis, KN, Ramanathan, RK, Baker, A, Aldrich, J, Kurdoglu, A, Izatt, T, Christoforides, A, Cherni, I, Nasser, S, Reiman, R, Cuyugan, L, McDonald, J, Adkins, J, Mastrian, SD, Valdez, R, Jaroszewski, DE, Von Hoff, DD, Craig, DW, Stewart, AK, Carpten, JD & Bryce, AH 2016, 'Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers', Scientific Reports, vol. 6, no. 1, 25. https://doi.org/10.1038/s41598-016-0021-4
Borad, Mitesh J ; Egan, Jan B. ; Condjella, Rachel M. ; Liang, Winnie S. ; Fonseca, Rafael ; Ritacca, Nicole R. ; McCullough, Ann E. ; Barrett, Michael ; Hunt, Katherine S. ; Champion, Mia D. ; Patel, Maitray D. ; Young, Scott W. ; Silva, Alvin C ; Ho, Thai H ; Halfdanarson, Thorvardur R. ; Mc Williams, Robert R ; Lazaridis, Konstantinos N ; Ramanathan, Ramesk K ; Baker, Angela ; Aldrich, Jessica ; Kurdoglu, Ahmet ; Izatt, Tyler ; Christoforides, Alexis ; Cherni, Irene ; Nasser, Sara ; Reiman, Rebecca ; Cuyugan, Lori ; McDonald, Jacquelyn ; Adkins, Jonathan ; Mastrian, Stephen D. ; Valdez, Riccardo ; Jaroszewski, Dawn E. ; Von Hoff, Daniel D. ; Craig, David W. ; Stewart, Alexander Keith ; Carpten, John D. ; Bryce, Alan H. / Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers. In: Scientific Reports. 2016 ; Vol. 6, No. 1.
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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.",
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AU - Borad, Mitesh J

AU - Egan, Jan B.

AU - Condjella, Rachel M.

AU - Liang, Winnie S.

AU - Fonseca, Rafael

AU - Ritacca, Nicole R.

AU - McCullough, Ann E.

AU - Barrett, Michael

AU - Hunt, Katherine S.

AU - Champion, Mia D.

AU - Patel, Maitray D.

AU - Young, Scott W.

AU - Silva, Alvin C

AU - Ho, Thai H

AU - Halfdanarson, Thorvardur R.

AU - Mc Williams, Robert R

AU - Lazaridis, Konstantinos N

AU - Ramanathan, Ramesk K

AU - Baker, Angela

AU - Aldrich, Jessica

AU - Kurdoglu, Ahmet

AU - Izatt, Tyler

AU - Christoforides, Alexis

AU - Cherni, Irene

AU - Nasser, Sara

AU - Reiman, Rebecca

AU - Cuyugan, Lori

AU - McDonald, Jacquelyn

AU - Adkins, Jonathan

AU - Mastrian, Stephen D.

AU - Valdez, Riccardo

AU - Jaroszewski, Dawn E.

AU - Von Hoff, Daniel D.

AU - Craig, David W.

AU - Stewart, Alexander Keith

AU - Carpten, John D.

AU - Bryce, Alan H

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