title: Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs).
abstract: OBJECTIVE
  To analyze the outcomes of treatment and factors predicting effects of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors (GIST) CD117(+) patients.
  
  
  METHODS
  We identified 232 patients in a prospectively collected Clinical GIST Registry with advanced inoperable/metastatic GIST treated with IM 400-800 mg daily (129 males and 103 females and median age 56 years). Median follow-up time was 26 months.
  
  
  RESULTS
  The estimated 3-year progression-free survival (PFS; calculated from the date of the start of IM) was 54% and median PFS was 40.5 months. The following factors significantly and negatively influenced PFS in univariate analysis: poor baseline World Health Organization (WHO) performance status > or = 2 (P < 0.00001), tumor genotype indicating other than KIT exon 11 isoform (P = 0.005), baseline high neutrophils count (P < 0.00001), age <45 years at the diagnosis (P = 0.04), mitotic index >10/50 high-power fields (HPF) (P = 0.001), GIST histological type other than spindle-cell (P = 0.03), baseline low albumin level (P = 0.0005), low baseline hemoglobin level (P < 0.00001), and primary overtly malignant tumors (unresectable and/or metastatic lesions at presentation) (P = 0.05). We identified four factors negatively affecting PFS, statistically significant (P < 0.05) in multivariate analysis: baseline poor WHO performance status > or = 2, high baseline neutrophils count (>5 x 10(9)/l), tumor genotype indicating the presence of non-exon 11 KIT mutant and mitotic index >10/50 HPF.
  
  
  CONCLUSIONS
  We confirmed that many advanced GIST patients benefit from IM therapy for a prolonged time, although resistance to therapy is observed. We identified four independent biological factors influencing the PFS during long-term IM therapy.
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland. rutkowskip@coi.waw.pl
authors: Piotr
authors: P
authors: Rutkowski
authors: Zbigniew I
authors: ZI
authors: Nowecki
authors: Maria
authors: M
authors: Debiec-Rychter
authors: Urszula
authors: U
authors: Grzesiakowska
authors: Wanda
authors: W
authors: Michej
authors: Agnieszka
authors: A
authors: Woźniak
authors: Janusz A
authors: JA
authors: Siedlecki
authors: Janusz
authors: J
authors: Limon
authors: Anna Jerzak
authors: AJ
authors: vel Dobosz
authors: Michał
authors: M
authors: Kakol
authors: Czesław
authors: C
authors: Osuch
authors: Włodzimierz
authors: W
authors: Ruka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D019089:Stem Cell Factor / Q000235:genetics; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D019089:Stem Cell Factor; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha