title: Impact of genomic profiling on the treatment and outcomes of patients with advanced gastrointestinal malignancies.
abstract: The impact of genomic profiling on the outcomes of patients with advanced gastrointestinal (GI) malignancies remains unknown. The primary objectives of the study were to investigate the clinical benefit of genomic-guided therapy, defined as complete response (CR), partial response (PR), or stable disease (SD) at 3 months, and its impact on progression-free survival (PFS) in patients with advanced GI malignancies. Clinical and genomic data of all consecutive GI tumor samples from April, 2013 to April, 2016 sequenced by FoundationOne were obtained and analyzed. A total of 101 samples from 97 patients were analyzed. Ninety-eight samples from 95 patients could be amplified making this approach feasible in 97% of the samples. After removing duplicates, 95 samples from 95 patients were included in the further analysis. Median time from specimen collection to reporting was 11 days. Genomic alteration-guided treatment recommendations were considered new and clinically relevant in 38% (36/95) of the patients. Rapid decline in functional status was noted in 25% (9/36) of these patients who could therefore not receive genomic-guided therapy. Genomic-guided therapy was utilized in 13 patients (13.7%) and 7 patients (7.4%) experienced clinical benefit (6 PR and 1 SD). Among these seven patients, median PFS was 10 months with some ongoing durable responses. Genomic profiling-guided therapy can lead to clinical benefit in a subset of patients with advanced GI malignancies. Attempting genomic profiling earlier in the course of treatment prior to functional decline may allow more patients to benefit from these therapies.
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Mashaal
authors.identifier: 0000-0002-1426-1098
authors.initials: M
authors.lastname: Dhir
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Haroon A
authors.initials: HA
authors.lastname: Choudry
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Holtzman
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: James F
authors.initials: JF
authors.lastname: Pingpank
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Ahrendt
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Amer H
authors.initials: AH
authors.lastname: Zureikat
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Hogg
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.affiliation: Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.affiliation: Division of Gastrointestinal Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Aatur D
authors.initials: AD
authors.lastname: Singhi
authors.affiliation: Division of Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15232.
authors.forename: Nathan
authors.initials: N
authors.lastname: Bahary
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000628:therapy*; D023281:Genomics / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010180:Pancreatectomy / Q000379:methods*; D057285:Precision Medicine; D017422:Sequence Analysis, DNA / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077146:Irinotecan; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Clinical benefit; gastrointestinal malignancies; genomic-guided therapy; genomics; precision medicine