title: Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib.
abstract: BACKGROUND
  Little is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib.
  
  
  METHODS
  Risk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high-risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months.
  
  
  RESULTS
  Five factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence-free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5-year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P < .001 for each comparison).
  
  
  CONCLUSIONS
  The scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.forename: Kirsten Sundby
authors.initials: KS
authors.lastname: Hall
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Pink
authors.forename: Jochen
authors.initials: J
authors.lastname: Schütte
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.forename: Marcus
authors.initials: M
authors.lastname: Schlemmer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Maarit
authors.initials: M
authors.lastname: Sarlomo-Rikala
authors.forename: Bengt
authors.initials: B
authors.lastname: Nilsson
authors.forename: Harri
authors.initials: H
authors.lastname: Sihto
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Peter
authors.initials: P
authors.lastname: Reichardt
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: adjuvant therapy; gastrointestinal stromal tumor; imatinib; predictive score
references.citation: Cancer. 2008 Feb 1;112(3):608-15
references.pmid: 18076015
references.citation: Biostatistics. 2004 Jul;5(3):465-81
references.pmid: 15208206
references.citation: Science. 2003 Jan 31;299(5607):708-10
references.pmid: 12522257
references.citation: Hum Pathol. 2002 May;33(5):459-65
references.pmid: 12094370
references.citation: Lancet Oncol. 2012 Mar;13(3):265-74
references.pmid: 22153892
references.citation: Lancet. 2009 Mar 28;373(9669):1097-104
references.pmid: 19303137
references.citation: Lancet. 2013 Sep 14;382(9896):973-83
references.pmid: 23623056
references.citation: Ann Oncol. 2012 Oct;23 Suppl 7:vii49-55
references.pmid: 22997454
references.citation: JAMA. 2012 Mar 28;307(12):1265-72
references.pmid: 22453568
references.citation: Int J Surg Pathol. 2005 Apr;13(2):161-5
references.pmid: 15864379
references.citation: JAMA. 1982 May 14;247(18):2543-6
references.pmid: 7069920
references.citation: Ann Surg. 2013 Sep;258(3):422-9
references.pmid: 23860199
references.citation: Ann Surg Oncol. 2006 Dec;13(12):1633-44
references.pmid: 17013685
references.citation: J Clin Pathol. 1990 Jul;43(7):597-9
references.pmid: 2199539
references.citation: Gastroenterology. 2003 Sep;125(3):660-7
references.pmid: 12949711
references.citation: Virchows Arch. 2012 Feb;460(2):163-9
references.pmid: 22190007
references.citation: Nat Rev Cancer. 2011 Nov 17;11(12):865-78
references.pmid: 22089421