title: Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor.
abstract: OBJECTIVE
  Benefit of adjuvant imatinib therapy following curative resection in patients with intermediate-risk gastrointestinal stromal tumor (GIST) is unclear. GIST-specific exon mutations, in particular exon 11 deletions, have been shown to be prognostic. We hypothesize that specific KIT mutations may improve risk stratification in patients with intermediate-risk GIST, identifying a subgroup of patients who may benefit from adjuvant therapy.
  
  
  METHODS
  In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included. Risk classification was based on the modified National Institute of Health (NIH) criteria.
  
  
  RESULTS
  In this cohort, 74% (n = 105) of patients harbored a KIT mutation; 61% (n = 86) were found in exon 11 of which nearly 70% were KIT exon 11 deletions (n = 60). A total of 18% (n = 25) of cases were classified as having intermediate-risk disease. Univariate analysis confirmed tumor size, mitotic index, nongastric origin, presence of tumor rupture and modified NIH criteria were adversely prognostic for relapse-free survival (RFS). Among KIT/PDGFRA mutants, KIT exon 11 deletions had a significantly worse prognosis (hazard ratio 2.31; 95% confidence interval, 1.30-4.10; P = 0.003). Multivariate analysis confirmed KIT exon 11 deletion (P = 0.003) and clinical risk classification (P < 0.001) as independent adverse prognostic factors for RFS. Intermediate-risk patients harboring KIT exon 11 deletions had RFS outcomes similar to high-risk patients.
  
  
  CONCLUSIONS
  The presence of KIT exon 11 deletion mutation in patients with intermediate-risk GIST is associated with an inferior clinical outcome with RFS similar to high-risk patients.
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.|Duke-NUS Graduate Medical School, Singapore.
authors.forename: Richard
authors.initials: R
authors.lastname: Quek
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Farid
authors.affiliation: Department of Medical Oncology, The Canberra Hospital, Garran, Australia.
authors.forename: Yada
authors.initials: Y
authors.lastname: Kanjanapan
authors.affiliation: Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore.
authors.forename: Cindy
authors.initials: C
authors.lastname: Lim
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.|Duke-NUS Graduate Medical School, Singapore.|Genome Institute of Singapore, Singapore.
authors.forename: Iain Beehuat
authors.initials: IB
authors.lastname: Tan
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Sittampalam
authors.initials: S
authors.lastname: Kesavan
authors.affiliation: Duke-NUS Graduate Medical School, Singapore.|Department of Pathology, Singapore General Hospital, Singapore.|School of Biological Sciences, Nanyang Technological University Singapore, Singapore.
authors.forename: Tony Kiat Hon
authors.initials: TKH
authors.lastname: Lim
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Lynette Lin-Ean
authors.initials: LL
authors.lastname: Oon
authors.affiliation: Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore.
authors.forename: Brian Kp
authors.initials: BK
authors.lastname: Goh
authors.affiliation: Department of Surgery, Singapore General Hospital, Singapore.
authors.forename: Weng Hoong
authors.initials: WH
authors.lastname: Chan
authors.affiliation: Division of Surgical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Melissa
authors.initials: M
authors.lastname: Teo
authors.affiliation: Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore.
authors.forename: Alexander Yf
authors.initials: AY
authors.lastname: Chung
authors.affiliation: Department of Upper GI and Bariatric Surgery, Singapore General Hospital, Singapore.
authors.forename: Hock Soo
authors.initials: HS
authors.lastname: Ong
authors.affiliation: Department of Upper GI and Bariatric Surgery, Singapore General Hospital, Singapore.
authors.forename: Wai Keong
authors.initials: WK
authors.lastname: Wong
authors.affiliation: Genome Institute of Singapore, Singapore.|Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.|Center for Translational Medicine, Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Medical Oncology, The Canberra Hospital, Garran, Australia.|ANU Medical School, Australian National University, Acton, Canberra, Australia.
authors.forename: Desmond
authors.initials: D
authors.lastname: Yip
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012189:Retrospective Studies; D017384:Sequence Deletion
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: GIST; KIT mutation; intermediate risk; prognostic factor