title: 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 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.
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA. borad.mitesh@mayo.edu.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA. borad.mitesh@mayo.edu.|Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. borad.mitesh@mayo.edu.
authors.forename: Mitesh J
authors.initials: MJ
authors.lastname: Borad
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Egan
authors.affiliation: Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Condjella
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA.|Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Ritacca
authors.affiliation: Department of Pathology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: McCullough
authors.affiliation: Mayo Clinic Cancer Center, Scottsdale, AZ, USA.|Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Barrett
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Hunt
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.|Department of Biomedical Statistics and Informatics, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Mia D
authors.initials: MD
authors.lastname: Champion
authors.affiliation: Department of Radiology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Maitray D
authors.initials: MD
authors.lastname: Patel
authors.affiliation: Department of Radiology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Young
authors.affiliation: Department of Radiology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Silva
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA.|Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Thai H
authors.identifier: http://orcid.org/0000-0003-0023-2939
authors.initials: TH
authors.lastname: Ho
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA.|Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Thorvardur R
authors.initials: TR
authors.lastname: Halfdanarson
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.|Mayo Clinic Cancer Center, Rochester, MN, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Baker
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Aldrich
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kurdoglu
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Izatt
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Christoforides
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Cherni
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Nasser
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Reiman
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Cuyugan
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: McDonald
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Adkins
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Mastrian
authors.affiliation: Department of Pathology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdez
authors.affiliation: Department of Cardiovascular Surgery, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Jaroszewski
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Craig
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA.|Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.affiliation: Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Carpten
authors.affiliation: Division of Hematology/Oncology Mayo Clinic, Scottsdale, AZ, USA.|Mayo Clinic Cancer Center, Scottsdale, AZ, USA.|Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Bryce
mesh_terms: D003955:Diagnostic Tests, Routine / Q000379:methods*; D004351:Drug Resistance; D023281:Genomics / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D011446:Prospective Studies