title: Neoadjuvant Imatinib in Locally Advanced Gastrointestinal stromal Tumours, Will Kit Mutation Analysis Be a Pathfinder?
abstract: BACKGROUND
  Longer duration of neoadjuvant (NA) imatinib (IM) used for locally advanced (LA) gastrointestinal stromal tumours (GIST) is not based on biology of the tumour reflected by kit mutation analysis.
  
  
  METHODS
  LA or locally recurrent (LR) GIST treated with NA IM from May 2008 to March 2015 from a prospective database were included in the analysis. Archived formalin-fixed paraffin-embedded tissues (FFPE) were used for testing KIT exons 9, 11, 13 and 17 by PCR.
  
  
  RESULTS
  One hundred twenty-five patients with LA or LR GIST were treated with NA IM. Forty-five patients (36 %) had undergone c-kit mutation testing. Exon 11 was seen in 25 patients (55.5 %), 3 with exon 9 (6.7 %) and 2 with exon 13 (4.4 %). Twelve were wild type (26.6 %) and  3 (6.7 %) were declared uninterpretable. Response rate (RR) for the exon 11 mutants was higher than the non-exon 11 mutant group (84 vs. 40 %, p = 0.01). Disease stabilization rate (DSR) rates were also higher in the exon 11 subgroup than non-exon 11 group (92 vs. 75 %). Eighty-four per cent exon 11 and 75 % non-exon 11 mutants were surgical candidates. Patients undergoing surgery had significantly improved event free survival (EFS) (p < 0.001) compared to patients not undergoing surgery, with the same trend seen in OS (p = 0.021). Patients with a SD on response to NA IM had a lower EFS (p = 0.076) and OS compared to patients achieving CR/PR. There were no differences between the various exon variants in terms of outcomes and responses CONCLUSION: Upfront evaluation of kit mutation status may help us in delineating separate treatment strategies for potentially biologically different tumours and assessing the correct timing of surgery for this subset of GIST.
authors.affiliation: Department of Medical Oncology, TMH, Mumbai, 400012, India.
authors.forename: Anant
authors.initials: A
authors.lastname: Ramaswamy
authors.affiliation: Department of Medical Oncology, TMH, Mumbai, 400012, India. dr.vikas.ostwal@gmail.com.
authors.forename: Vikas
authors.initials: V
authors.lastname: Ostwal
authors.affiliation: Department of Pathology, TMH, Mumbai, 400012, India.
authors.forename: Omshree
authors.initials: O
authors.lastname: Shetty
authors.affiliation: Department of Medical Oncology, TMH, Mumbai, 400012, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Sahu
authors.affiliation: Department of Medical Oncology, TMH, Mumbai, 400012, India.
authors.forename: Davinder
authors.initials: D
authors.lastname: Paul
authors.affiliation: Department of Pathology, TMH, Mumbai, 400012, India.
authors.forename: Trupti
authors.initials: T
authors.lastname: Pai
authors.affiliation: Department of Pathology, TMH, Mumbai, 400012, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Gurav
authors.affiliation: Department of Interventional Radiology, TMH, Mumbai, 400012, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Shetty
authors.affiliation: Department of Surgical Oncology, TMH, Mumbai, 400012, India.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Shrikhande
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy / Q000379:methods*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate
keywords: Gist; KIT mutation analysis; Locally advanced; Neoadjuvant imatinib