title: Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial.
abstract: OBJECTIVE
  The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome.
  
  
  METHODS
  There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis.
  
  
  RESULTS
  RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model-adjusted P < .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival.
  
  
  CONCLUSIONS
  Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS.
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC. corlessc@ohsu.edu.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Violetta
authors.initials: V
authors.lastname: Kolesnikova
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Peter W T
authors.initials: PW
authors.lastname: Pisters
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Blackstein
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Martin D
authors.initials: MD
authors.lastname: McCarter
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.affiliation: Christopher L. Corless, Violetta Kolesnikova, Charles D. Blanke, Michael C. Heinrich, Oregon Health and Science University, Portland, OR; Karla V. Ballman, Mayo Clinic, Rochester, MN; Cristina R. Antonescu and Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center; Robert G. Maki, Mt Sinai School of Medicine, New York, NY; Peter W.T. Pisters and Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX; Martin E. Blackstein, Mount Sinai Hospital, Toronto, Ontario, Canada; George D. Demetri, Dana-Farber Cancer Institute, Boston, MA; Margaret von Mehren, Fox Chase Cancer Institute, Philadelphia, PA; Martin D. McCarter, University of Colorado School of Medicine, Aurora, CO; and Kouros Owzar, Duke University School of Medicine, Durham, NC.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D020022:Genetic Predisposition to Disease; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D010641:Phenotype; D010879:Piperazines / Q000008:administration & dosage*; D057285:Precision Medicine; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha