title: Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers.
abstract: METHODS
  Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS.
  
  
  RESULTS
  From April 2014-October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs. 3 of 57 (5.3%) treated with non-genomically guided therapy (p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy (p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84).
  
  
  CONCLUSIONS
  Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Milan
authors.initials: M
authors.lastname: Radovich
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Kiel
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Nance
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Niland
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Parsley
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.
authors.forename: Meagan E
authors.initials: ME
authors.lastname: Ferguson
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Guanglong
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Natraj R
authors.initials: NR
authors.lastname: Ammakkanavar
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Einhorn
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nassiri
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Davidson
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Rushing
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loehrer
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Nasser
authors.initials: N
authors.lastname: Hanna
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Callaghan
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Helft
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Safi
authors.initials: S
authors.lastname: Shahda
authors.affiliation: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
authors.affiliation: Indiana University Health Precision Genomics Program, Indianapolis, IN, USA.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Schneider
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007196:Indiana; D008297:Male; D008495:Medical Oncology / Q000379:methods*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000628:therapy; D057285:Precision Medicine / Q000379:methods*; D012107:Research Design; D012509:Sarcoma / Q000235:genetics / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000628:therapy; D016896:Treatment Outcome; D014495:Universities
keywords: genomics; next-generation sequencing; personalized medicine; precision medicine